STEP 7

1. Definition of organic mental disorder?

Didalam DSM IV diputusakan bahwa perbedaan lama antara gangguan
organik dan fungsional telah ketinggalan jaman dan dikeluarkan dari tata
nama. Bagian yang disebut Gangguan Mental Organik dalam DSM III-R
sekarang disebut sebagai Delirium, Demensia, Gangguan Amnestik Gangguan
Kognitif lain, dan Gangguan Mental karena suatu kondisi medis umum yang
tidak dapat diklasifikasikan di tempat lain.1

Menurut PPDGJ III gangguan mental organik meliputi berbagai gangguan

jiwa yang dikelompokkan atas dasar penyebab yang lama dan dapat
dibuktikan adanya penyakit, cedera atau ruda paksa otak, yang berakibat
disfungsi otak Disfungsi ini dapat primer seperti pada penyakit, cedera, dan
ruda paksa yang langsung atau diduga mengenai otak, atau sekunder, seperti
pada gangguan dan penyakit sistemik yang menyerang otak sebagai salah
satu dari beberapa organ atau sistem tubuh 4

PPDGJ II membedakan antara Sindroma Otak Organik dengan Gangguan

Mental Organik. Sindrom Otak Organik dipakai untuk menyatakan sindrom
(gejala) psikologik atau perilaku tanpa kaitan dengan etiologi. Gangguan
Mental Organik dipakai untuk Sindrom Otak Organik yang etiolognnya
(diduga) jelas Sindrom Otak Organik dikatakan akut atau menahun
berdasarkan dapat atau tidak dapat kembalinya (reversibilitas) gangguan
jaringan otak atau Sindrom Otak Organik itu dan akan berdasarkan
penyebabnya, permulaan gejala atau lamanya penyakit yang
menyebabkannya. Gejala utama Sindrom Otak Organik akut ialah kesadaran
yang menurun (delirium )dan sesudahnya terdapat amnesia, pada Sindrom
Otak Organik menahun (kronik) ialah demensia (PPDGJ, DSM)

2. What kind of organic mental disorder?

Gangguan mental organik merupakan gangguan-ganguan yang dikaitkan
dengan disfungsi otak secara temporer atau permanen. Oeh karena itu,
ganguan mental organik disebut juga organic brain syndromes, yang
dikelompokkan dalam 7 tipe (Choca, 1980), yaitu :

No. Nama Gangguan Karakteristik utama

1 Demensia Gangguan fungsi intelektual
2. Delirium Gangguan konsentrasi dan kesadaran
3. Sindrom amnesic Gangguan memori
4. Sindrom delusi Munculnya khayalan-khayalan
organic
5. Halusinasi organik Munculnya halusinasi
6. Sindrom mental Gangguang pada fungsi emosi
organik
7. Intoksikasi Gangguan intelektual dan fungsi
motorik
8. Withdrawals Gangguan intelektual czn fungsi
 motorik

Menurut PPDGJ III, klasifikasi gangguan mental organik adalah sebagai

berikut :

l. Demensia pada penyakit Alzheimer

1.1 Demensia pada penyakit Alzheimer dengan onset dini.

1.2.Demensia pada penvakit Alzheimer dengan onset lambat.

1.3.Demensia pada penyakit Alzheimer, tipe tak khas atau tipe campuran.

1.4. Demensia pada penyakit Alzheimer Yang tidak tergolongkan ( YTT).

2. Demensia Vaskular

2.1.Demensia Vaskular onset akut.

2.2. Demensia multi-infark

2.3 Demensia Vaskular subkortikal.

2.4. Demensia Vaskular campuran kortikal dan subkortikal

2.5. Demensia Vaskular lainnya

2.6. Demensia Vaskular YTT

3. Demensia pada penyakit lain yang diklasifikasikan di tempat lain (YDK)

3.1. Demensia pada penyakit Pick.

3.2. Demensia pada penyakit Creutzfeldt Jakob.

3. 3. Demensia pada penyakit huntington.

3.4. Demensia pada penyakit Parkinson.

3.5. Demensia pada penyakit human immunodeciency virus (HIV).

3.6. Demensia pada penyakit lain yang ditentukan (YDT) dan YDK

4. Demensia YTT.

Karakter kelima dapat digunakan untuk menentukan demensia pada 1-4 sebagai
berikut :

1. Tanpa gejala tambahan.

2. Gejala lain, terutama waham.

3. Gejala lain, terutama halusinasi

4. Gejala lain, terutama depresi

5. Gejala campuran lain.

5. Sindrom amnestik organik bukan akibat alkohol dan zat psikoaktif lainnya

6. Delirium bukan akibat alkohol dan psikoaktif lain nya

6.1. Delirium, tak bertumpang tindih dengan demensia

6.2. Delirium, bertumpang tindih dengan demensia

6. 3. Delirium lainya.

6.4 DeliriumYTT.

7. Gangguan mental lainnya akibat kerusakan dan disfungsi otak dan penyakit
fisik.

7.1. Halusinosis organik.

7.2. Gangguan katatonik organik.

7.3. Gangguan waham organik (lir-skizofrenia)

7.4. Gangguan suasana perasaan (mood, afektif) organik.

7.4.1. Gangguan manik organik.

7.4.2. Gangguan bipolar organik.

7.4.3. Gangguan depresif organik.

7.4.4. Gangguan afektif organik campuran.

7.5. Gangguan anxietas organik

7.6. Gangguan disosiatif organik.

7.7. Gangguan astenik organik.

7.8. Gangguan kopnitif ringan.

7.9. Gangguan mental akibat kerusakan dan disfungsi otak dan penyakit fisik lain
YDT.

7.10. Gangguan mental akibat kerusakan dan disfungsi otak dan penyakit fisik
YTT.
8. Gangguan keperibadian dan prilaku akibat penyakit, kerusakan dan fungsi
otak

8.1. Gangguan keperibadian organik

8.2. Sindrom pasca-ensefalitis

8.3. Sindrom pasca-kontusio

8.4. Gangguan kepribadian dan perilaku organik akibat penyakit, kerusakan dan
disfungsi otak lainnya.

8.5. Gangguan kepribadian dan perilaku organik akibat penyakit, kerusakan dan
disfungsi otak YTT.

9. Gangguan mental organik atau simtomatik YTT

Menurut Maramis, klasifikasi gangguan mental organik adalah sebagai berikut:

1. Demensia dan Delirium

2. Sindrom otak organik karena rudapaksa kepala.

3. Aterosklerosis otak

4. Demensia senilis

5. Demensia presenilis.

6. Demensia paralitika.

7. Sindrom otak organik karena epilepsi.

8. Sindrom otak organik karena defisiensi vitamin, gangguan metabolisme

dan intoksikasi.

9. Sindrom otak organik karena tumor intra kranial.

Menurut DSM IV, klasifikasi gangguan mental organik sebagai berikut:

1. Delirium

1.1. Delirium karena kondisi medis umum.

1.2. Delirium akibat zat.

1.3. Delirium yang tidak ditentukan (YTT)

2. Demensia.
2.1. Demensia tipe Alzheimer.

2.2. Demensia vaskular.

2.3. Demensia karena kondisi umum.

2.3.1. Demensia karena penyakit HIV.

2.3.2. Demensia karena penyakit trauma kepala.

2.3.3. Demensia karena penyakit Parkinson.

2.3.4. Demensia karena penyakit Huntington.

2.3.5. Demensia karena penyakit Pick

2.3.6. Demensia karena penyakit Creutzfeldt Jakob

2.4. Demensia menetap akibat zat

2.5. Demensia karena penyebab multipeL

2.6. Demensia yang tidak ditentukan (YTT)

3. Gangguan amnestik

3.1.Gangguan amnestik karena kondisi medis umum.

3.2 Gangguan amnestik menetap akibat zat

3.3 Gangguan amnestik yang tidak ditentukan ( YTT )

4. Gangguan kognitif yang tidak ditentukan.

3. What are the etiology of Organic Mental Disorder?

Etiologi Primer berasal dari suatu penyakit di otak dan suatu cedera atau
rudapaksa otak atau dapat dikatakan disfungsi otak. Sedangkan etiologi
sekunder berasal dari penyakit sistemik yang menyerang otak sebagai salah
satu dari beberapa organ atau sistem tubuh.
Istilah organik merupakan sindrom yang diklasifikasikan dapat berkaitan
dengan gangguan/penyakit sistemik/otak yang secara bebas dapat
didiagnosis. Sedangkan istilah simtomatik untuk GMO yang pengaruhnya
terhadap otak merupakan akibat sekunder dari gangguan / penyakit ekstra
serebral sitemik seperti zat toksik berpengaruh pada otak bisa bersifat
sesaat/jangka panjang.
4. What are the differen between Dementia and Delirium, amnesia?

Gambaran Delirium Demensia

Riwayat Penyakit akut Penyakit kronik

Awal Cepat Lambat laun

Sebab Terdapat penyakit lain (infeksi, Biasanya penyakit otak kronik

dehidrasi, guna/putus obat (spt Alzheimer, demensia
vaskular)

Lamanya Ber-hari/-minggu Ber-bulan/-tahun

Perjalanan sakit Naik turun Kronik progresif

Taraf kesadaran Naik turun Normal

Orientasi Terganggu, periodik Intak pada awalnya

Afek Cemas dan iritabel Labil tapi tak cemas

Alam pikiran Sering terganggu Turun jumlahnya

Bahasa Lamban, inkoheren, inadekuat Sulit menemukan istilah tepat

Daya ingat Jangka pendek terganggu nyata Jangka pendek & panjang
terganggu

Persepsi Halusinasi (visual) Halusinasi jarang kecuali

sundowning

Psikomotor Retardasi, agitasi, campuran Normal

Tidur Terganggu siklusnya Sedikit terganggu siklus tidurnya

Atensi & Amat terganggu Sedikit terganggu

kesadaran

Reversibilitas Sering reversibel Umumnya tak reversibel

Penanganan Segera Perlu tapi tak segera

1. AMNESIA
Amnesia adalah suatu kondisi yang mengacu pada hilangnya memori, seperti
kejadian, informasi dan berbagai pengalaman. Meski terkadang ada penderita
amnesia yang tak tahu siapa diri mereka, seperti di tayangan film dan
televisi, namun secara umum kondisi itu tidak sampai memicu kehilangan
identitas diri. Sebenarnya para penderita amnesia, atau kerap disebut
amnestic syndrome, biasanya tahu siapa diri mereka. Tapi memang mereka
sulit menyerap informasi baru dan membangun memori baru.

Amnesia bisa disebabkan oleh kerusakan pada area di sekitar otak yang biasa
digunakan untuk proses mengingat. Dan tak seperti penderita yang
kehilangan memori untuk sementara waktu (transient global amnesia),
amnestic syndrome ini kemungkinan besar permanen. Sejauh ini tak ada
perlakuan khusus pada amnesia, namun sejumlah teknik untuk meningkatkan
daya ingat di samping upaya untuk mendukung mereka secara psikologis
diyakini cukup ampuh membantu penderita amnesia.

Gejala :
Ada dua hal utama pada penderita amnesia:
Gangguan kemampuan mempelajari atau menyerap informasi baru akibat
serangan amnesia (anterograde amnesia)
Gangguan kemampuan mengingat kembali kejadian-kejadian lalu dan
informasi yang baru diberikan (retrograde amnesia)

Gejala lain :
Ada juga tanda-tanda atau gejala lain dari amnesia, tapi ini tergantung pada
penyebabnya, seperti:
Kesalahan dalam pengumpulan memori (rekaan). Biasanya memori yang
sudah didapat kembali itu tak dapat disimpan sesuai dengan waktunya
Gangguan syaraf seperti gerakan-gerakan tak terkendali, gemetar dan juga
kejang-kejang
Kebingungan atau disorientasi

2. DEMENSIA
Demensia adalah penurunan kemampuan mental yang biasanya berkembang
secara perlahan, dimana terjadi gangguan ingatan, fikiran, penilaian dan
kemampuan untuk memusatkan perhatian, dan bisa terjadi kemunduran
kepribadian.

Pada usia muda, demensia bisa terjadi secara mendadak jika cedera hebat,
penyakit atau zat-zat racun (misalnya karbon monoksida) menyebabkan
hancurnya sel-sel otak. Tetapi demensia biasanya timbul secara perlahan dan
menyerang usia diatas 60 tahun. Namun demensia bukan merupakan bagian
dari proses penuaan yang normal. Sejalan dengan bertambahnya umur, maka
perubahan di dalam otak bisa menyebabkan hilangnya beberapa ingatan
(terutama ingatan jangka pendek) dan penurunan beberapa kemampuan
belajar. Perubahan normal ini tidak mempengaruhi fungsi.
 Lupa pada usia lanjut bukan merupakan pertanda dari demensia maupun
penyakit Alzheimer stadium awal. Demensia merupakan penurunan
kemampuan mental yang lebih serius, yang makin lama makin parah. Pada
penuaan normal, seseorang bisa lupa akan hal-hal yang detil; tetapi penderita
demensia bisa lupa akan keseluruhan peristiwa yang baru saja terjadi.

GEJALA
Demensia biasanya dimulai secara perlahan dan makin lama makin parah,
sehingga keadaan ini pada mulanya tidak disadari. Terjadi penurunan dalam
ingatan, kemampuan untuk mengingat waktu dan kemampuan untuk
mengenali orang, tempat dan benda.

Penderita memiliki kesulitan dalam menemukan dan menggunakan kata yang

tepat dan dalam pemikiran abstrak (misalnya dalam pemakaian angka).
Sering terjadi perubahan kepribadian.

Demensia karena penyakit Alzheimer biasanya dimulai secara samar. Gejala

awal biasanya adalah lupa akan peristiwa yang baru saja terjadi; tetapi bisa
juga bermula sebagai depresi, ketakutan, kecemasan, penurunan emosi atau
perubahan kepribadian lainnya.

Terjadi perubahan ringan dalam pola berbicara; penderita menggunakan kata-

kata yang lebih sederhana, menggunakan kata-kata yang tidak tepat atau
tidak mampu menemukan kata-kata yang tepat. Ketidakmampuan
mengartikan tanda-tanda bisa menimbulkan kesulitan dalam mengemudikan
kendaraan. Pada akhirnya penderita tidak dapat menjalankan fungsi
sosialnya.

Demensia karena stroke kecil memiliki perjalanan penyakit dengan pola

seperti menuruni tangga.
Gejalanya memburuk secara tiba-tiba, kemudian agak membaik dan
selanjutnya akan memburuk kembali ketika stroke yang berikutnya terjadi.
Mengendalikan tekanan darah tinggi dan kencing manis kadang dapat
mencegah stroke berikutnya dan kadang terjadi penyembuhan ringan.

Beberapa penderita bisa menyembunyikan kekurangan mereka dengan baik.

Mereka menghindari aktivitas yang rumit (misalnya membaca atau bekerja).
Penderita yang tidak berhasil merubah hidupnya bisa mengalami frustasi
karena ketidakmampuannya melakukan tugas sehari-hari. Penderita lupa
untuk melakukan tugasnya yang penting atau salah dalam melakukan
tugasnya.

3. DELIRIUM
Delirium adalah keadaan yang yang bersifat sementara dan biasanya terjadi
secara mendadak, dimana penderita mengalami penurunan kemampuan
dalam memusatkan perhatiannya dan menjadi linglung, mengalami
disorientasi dan tidak mampu berfikir secara jernih.

PENYEBAB
Delirium merupakan suatu keadaan mental yang abnormal, bukan suatu
penyakit; dengan sejumlah gejala yang menunjukkan penurunan fungsi
mental. Berbagai keadaan atau penyakit (mulai dari dehidrasi ringan sampai
keracunan obat atau infeksi yang bisa berakibat fatal), bisa menyebabkan
delirium.

Keadaan ini paling sering terjadi pada usia lanjut dan penderita yang otaknya
telah mengalami gangguan, termasuk orang yang sakit berat, orang yang
mengkonsumsi obat yang menyebabkan perubahan fikiran atau perilaku dan
orang yang mengalami demensia.

Penyebab Delirium:
a. Alkohol, obat-obatan dan bahan beracun
b. Efek toksik dari pengobatan.
c. Kadar elektrolit, garam dan mineral (misalnya kalsium, natrium atau
magnesium) yang tidak normal akibat pengobatan, dehidrasi atau penyakit
tertentu
d. Infeksi akut disertai demam
e. Hidrosefalus bertekanan normal, yaitu suatu keadaan dimana cairan yang
membantali otak tidak diserap sebagaimana mestinya dan menekan otak
f. Hematoma subdural, yaitu pengumpulan darah di bawah tengkorak yang
dapat menekan otak.
g. Meningitis, ensefalitis, sifilis (penyakit infeksi yang menyerang otak).
h. Kekurangan tiamin dan vitamin B12
i. Hipotiroidisme maupun hipotiroidisme
j. Tumor otak (beberapa diantaranya kadang menyebabkan linglung dan
gangguan ingatan)
k. Patah tulang panggul dan tulang-tulang panjang
l. Fungsi jantung atau paru-paru yang buruk dan menyebabkan rendahnya
kadar oksigen atau tingginya kadar karbon dioksida di dalam darah
m. Stroke.

GEJALA
Delirium dapat diawali dengan berbagai gejala, dan kasus yang ringan
mungkin sulit untuk dikenali.
Tingkah laku seseorang yang mengalami delirium bervariasi, tetapi kira-kira
sama seperti orang yang sedang mengalami mabuk berat. Ciri utama dari
delirium adalah tidak mampu memusatkan perhatian.
Penderita tidak dapat berkonsentrasi, sehingga mereka memiliki kesulitan
dalam mengolah informasi yang baru dan tidak dapat mengingat peristiwa
yang baru saja terjadi.

Hampir semua penderita mengalami disorientasi waktu dan bingung dengan

tempat dimana mereka berada. Fikiran mereka kacau, mengigau dan terjadi
 inkoherensia.

Pada kasus yang berat, penderita tidak mengetahui diri mereka sendiri.
Beberapa penderita mengalami paranoia dan delusi (percaya bahwa sedang
terjadi hal-hal yang aneh). Respon penderita terhadap kesulitan yang
dihadapinya berbeda-beda; ada yang sangat tenang dan menarik diri,
sedangkan yang lainnya menjadi hiperaktif dan mencoba melawan halusinasi
maupun delusi yang dialaminya.

Jika penyebabnya adalah obat-obatan, maka sering terjadi perubahan

perilaku. Keracunan obat tidur menyebabkan penderita sangat pendiam dan
menarik diri, sedangkan keracunan amfetamin menyebabkan penderita
menjadi agresif dan hiperaktif.

Delirium bisa berlangsung selama berjam-jam, berhari-hari atau bahkan lebih

lama lagi, tergantung kepada beratnya gejala dan lingkungan medis
penderita. Delirium sering bertambah parah pada malam hari (suatu
fenomena yang dikenal sebagai matahari terbenam). Pada akhirnya,
penderita akan tidur gelisah dan bisa berkembang menjadi koma (tergantung
kepada penyebabnya).

5. What are patofisiology of each organic mental disorder clasification?

DELIRIUM
(Maldonado, J.R., et al., Dexmedetomidine and the reduction of postoperative
delirium after cardiac surgery. Psychosomatics, 2009)
The response of the brain to systemic infection is physiologically
triggered by an activating signal that is mediated by three pathways. 1)
The neural pathway that requires activation of primary afferent nerves, such as
the vagal or the trigeminal nerves, by involving peripherally produced pathogen-
associated molecular patterns (PAMPs) and cytokines. 2) The humoral pathway
involves circulating cytokines. They reach the brain at the level of the choroid
plexus and the circumventricular organs that lie outside the bloodbrain barrier
(BBB). 3) The bloodbrain barrier alterations induced by the activation of cerebral
endothelial cells results in the release of various mediators into the brain. This
activation is due to the production, at the early phase of sepsis, of nitric oxide
synthase-derived nitric oxide. All of these pathways instigate the activation of
microglial cells, which are the resident immune cells of the brain. When
activated, microglial cells may negatively affect the brain by the production of
nitric oxide, cytokines, and reactive oxygen species that lead to cell death within
vulnerable areas of the brain. This production is, in itself, responsible for an
increase of the BBB alterations, thus causing a vicious circle of increasing brain
dysfunction and injury. These mechanisms are compounded by common
metabolic disturbances that occur in septic patients (such as prolonged
hyperglycemia, severe hypoxemia), hemodynamic failure, use of medications,
and iatrogenic and environmental factors. Septic-associated brain dysfunction
may be associated with neurologic sequelae in survivors, including functional
and cognitive decline, probably by neurodegenerative and/or ischemic
mechanisms.
Brain signaling and microglial activation
The encephalopathy in sepsis is considered a diffuse cerebral dysfunction as a consequence of
the systemic inflammatory response to an infection, with no direct central nervous system
infection (Figure 1). The response to stress is physiologically triggered by an activating signal
that is mediated by two pathways. The first one is the vagus nerve, which can detect visceral
inflammation through its axonal cytokines receptors: inflammatory products produced in
damaged tissues activate afferent signals that are relayed to the nucleus tractus solitarius in
the brainstem. Subsequent activation of vagus efferent activity inhibits cytokine synthesis in
damaged tissues through a cholinergic anti-inflammatory pathway (the inflammatory reflex)
[8]. The vagus nerve is also connected to other autonomic nuclei, notably the paraventricular
nucleus that controls adrenal axis and vasopressin secretion [9]. The second pathway involves
the circumventricular organs (CVOs), which are located near neuroendocrine and
neurovegetative nuclei. CVOs are deprived of a bloodbrain barrier (BBB) and express
components of innate and adaptive immune systems. Once visceral or systemic inflammation
is detected by the first or the second pathway, the activating signal will spread to behavioral,
neuroendocrine, and neurovegetative centers. Sepsis enhances the transcription of several
pro- and anti-inflammatory cytokines and chemokines in the brain, including tumor necrosis
factor alpha (TNF), interleukin-1 beta (IL1), transforming growth factor beta (TGF ), and
monocyte chemoattractant protein 1 (MCP1) [10]. These mediators modulate the expression
of -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and N-
methyl-D-aspartate receptors (NMDARs) on neurons, inducing brain dysfunction [11].
Recent studies have suggested the novel importances of IL1 and High Mobility Group Box
1 on the development of cognitive impairment in sepsis survivors [12,13]. These cytokines
also modulate NMDARs, with functional consequences on cognition and behavior [14].

Microglial activation may represent one of the earliest changes observed in sepsis-associated
encephalopathy and prolonged microglial activation may negatively affect other brain cells
[15]. Early microglial activation in sepsis was evidenced in mice models within 4 hours
following LPS injection, as assessed by the increased proinflammatory cytokine IL1 level in
microglia [16]. Using Positron Emission Tomography (PET) imaging in nonhuman primates,
another study demonstrated microglia activation only 1h after LPS-induced systemic
inflammation [17]. Moreover, experimental studies suggest that aging may increase the
intensity of microglial activation and the production proinflammatory cytokines in the
hippocampus, notably IL1 [18,19]. The IL1-mediated inflammatory process in the
hippocampus was confirmed in different models of systemic inflammation, including cecal
ligation and puncture and peripheral surgery [20,21]. Numerous experimental studies suggest
that these proinflammatory mediators released in the central nervous system at the onset of
sepsis will in turn lead to neuronal loss within vulnerable areas of the brain, including the
hippocampus [22-24]. Collectively, these findings represent a neuropathological basis for
persistent cognitive impairment, hippocampal atrophy, and electroencephalographic changes
observed in sepsis survivors [25].
Endothelial activation and bloodbrain barrier dysfunction
Sepsis induces activation of cerebral endothelial cells, which result in BBB dysfunction and
release of various mediators into the brain. Experimental data indicate that at the early phase
of sepsis, endothelial nitric oxide synthase-derived nitric oxide exhibits proinflammatory
characteristics and contributes to the activation and dysfunction of cerebrovascular
endothelial cells [26]. The activated endothelium relays the inflammatory response into the
brain by releasing proinflammatory cytokines and NO that are able to interact with
surrounding brain cells. The other consequences of endothelial activation may include
microcirculatory dysfunction, which might compromise cerebral perfusion [27]. Other studies
suggest that endotoxemia leads to inflammation in brain, with alteration in BBB, up-
regulation of aquaporin 4 (AQP4) and associated edema, neutrophil infiltration, astrocyte
activation, as well as apoptotic cell death, all of which appear to be mediated by TNF-alpha
signaling through TNF-receptor 1 [28]. Alterations of BBB also have been evidenced in
patients with septic shock, with help of brain MRI [29]. BBB breakdown can be localized in
the cortex around the Virchow-Robin spaces or have a more diffuse pattern in the whole
white matter. It also can predominate in posterior lobes, being consistent with a posterior
reversible encephalopathy syndrome [30]. Noninvasive assessment by MRI allowed the
identification of new aspects of brain damage in experimental models of sepsis, including
cytotoxic and vasogenic edema as well as neuronal damage. These findings highlight the
potential applications of MRI techniques for the diagnostic and therapeutic studies in sepsis
[31]. Finally, BBB alterations might facilitate the passage of potential neurotoxic factors from
the peripheral circulation to the brain. For instance, plasma tryptophan levels are associated
with delirium in critically ill patients [32,33]. More recently, increased kynurenine pathway
activation, assessed by plasma kynurenine and kynurenine/tryptophan ratio, was found to be
associated with fewer days without acute brain dysfunction [33].

Endothelial activation alters vascular tone and induces both microcirculatory dysfunction and
coagulopathy, which will in turn favor ischemic and/or hemorrhagic lesions [34].
Neuropathological studies performed in nonsurvivors of septic shock suggest that ischemia is
consistently observed in brain areas susceptible to low cerebral flow and that hemorrhages
can be found in approximately 10% of cases [34,35]. Furthermore, it has been recently shown
that SAE is rather associated with disturbed autoregulation than with altered cerebral blood
flow or tissue oxygenation [36].

Deficit in cholinergic function and alteration of neurotransmission

Deficits in cholinergic function have been postulated to cause delirium and cognitive decline
[37]. Global hypocholinergia result from several mechanisms, including impaired
acetylcholine synthesis and cholinergic synaptic dysfunction (impairment of presynaptic,
synaptic, or postsynaptic functions of acetylcholine). Nicotinic receptors within the brain
bind acetylcholine to modulate cognitive functioning, arousal learning, and memory. Use of
anesthetic drugs that decrease acetylcholine release (e.g., isoflurane) may impact on cognitive
function after surgery [38]. Anticholinergic medications and their metabolites also may
induce delirium through competitive antagonism of postsynaptic muscarinic receptors that are
more widely distributed throughout the brain. It was recently demonstrated that chronic
cholinergic hypoactivity in the basal forebrain represents a major factor of acute brain
dysfunction under systemic inflammation [39].

Other significant neurotransmitter alterations have been described during experimental sepsis,
involving brain beta-adrenergic, gamma-aminobutyric acid, and serotoninergic pathways
[40]. These phenomena seem to predominate in cortex and in hippocampus, and may be
mediated by NO, cytokines and prostaglandins [41]. Neurotransmitter balance also is altered
by different circulating molecules, such as ammonium, tyrosine, tryptophan, and
phenylalanine, whose plasma levels are increased secondary to liver dysfunction and muscle
proteolysis [42]. Imbalance between dopaminergic and cholinergic neurotransmission is
considered a major mechanism of delirium in critically ill patients. It also has been
hypothesized that reduced cholinergic inhibition of microglia is involved in delirium [15].
However, administration of rivastigmine, a pharmacological agent that may restore
cholinergic control of microglia, did not decrease duration of delirium and might have
increased mortality of critically ill patients with delirium [43]. Data from studies performed
in critically ill patients receiving prolonged mechanical ventilation also suggest that use of
GABA-agonists, such as benzodiazepines, is associated with an increased risk of brain
dysfunction [44]. Noradrenergic neurotransmission also might be particularly involved in
SAE as dexmedetomidine, a selective agonist of alpha2-adrenoceptors expressed in the locus
coeruleus, is associated with less brain dysfunction and better outcomes in septic patients
compared with midazolam [45,46]. These findings were recently confirmed in a recent,
multicenter trial, where dexmedetomidine compared with midazolam, improved patients
ability to communicate [47]. Beneficial effects of dexmedetomidine notably include
significant preconditioning and postconditioning effects against ischemic brain injury
[48,49]. More recent experimental data suggested that neuroprotective effects of
dexmedetomidine against glutamate-induced cell death were mediated by an increase in
astrocyte expression of brain-derived neurotrophic factor through an extracellular signal-
regulated kinase-dependent pathway [50].

Oxidative stress, mitochondrial dysfunction, and apoptosis

Experimental data suggest that oxidative damage, assessed by the thiobarbituric acid reactive
species and the protein carbonyl assays, occurs early (after 6 hours) in the course of sepsis
[51]. Moreover, the combined use of antioxidants (N-acetyl-cysteine and deferoxamine)
attenuates oxidative damage in hippocampus 6 hours after sepsis induction [52].
Mitochondrial-mediated apoptosis has been evidenced in experimental sepsis and might be
related to a decrease of intracellular anti-apoptotic (bcl-2) and an increase of pro-apoptotic
(bax) factors [22]. In patients who had died from septic shock, neuronal and microglial
apoptosis have been detected in neurovegetative and neuroendocrine nuclei as well as in
amygdala [35]. Intensity of apoptosis correlated with expression of endothelial iNOS. Recent
data suggested that Caspase-3 is involved in part in apoptosis in the dentate gyrus cell layer
of the hippocampus in septic rats [53]. Additionally to nitric oxide, other pro-apoptotic
factors have been incriminated, such as glutamate, TNF, and hyperglycemia [54].
Prolonged inflammation and other systemic insults
A recent study performed in critically ill patients suggested that high baseline inflammatory
biomarkers of systemic inflammation at admission, such as C-reactive protein and
procalcitonin, predicted prolonged periods of acute brain dysfunction, irrespective of whether
patients had sepsis or not [55]. In another study performed in 50 patients with systemic
inflammatory response syndrome (SIRS), IL-8 was independently associated with delirium
[56]. These findings suggest that sustained systemic inflammation may contribute to prolong
or aggravate brain dysfunction. Stress hyperglycemia, which commonly develops in critically
ill patients, also may aggravate sepsis-induced brain injury. In a recent neuropathological
study performed in nonsurvivors of critical illness, hyperglycemia was shown to aggravate
critical illness-induced neuropathological changes [57]. Patients with uncontrolled
hyperglycemia showed increased microglial activation, an important reduction in the density
and activation status of astrocytes, increased neuronal damage, and apoptosis in hippocampus
and frontal cortex. Most of these abnormalities were virtually absent with normoglycemia.
Interestingly, moderate hyperglycemia was shown to be associated with adverse cognitive
outcomes in survivors of the acute respiratory distress syndrome [58]. Prolonged hypoxemia
also may contribute to brain dysfunction and injury during sepsis. Recently, in a study
performed in survivors of prolonged critical illness, a low partial pressure of arterial oxygen
during ICU stay was associated with cognitive and psychiatric impairment at 12 months [59].

Selective vulnerability
Brain lesions in septic shock have been described in areas of the brain susceptible to ischemia
(including Ammons horn, the frontal junctional cortex, the lenticular nuclei, the dentate
nucleus, and the medullary olive), in the hypothalamic nuclei (supraoptic and paraventricular
nuclei), the amygdala, the locus coeruleus, and the medullary autonomic nuclei (nucleus
tractus solitarii, ambiguous, and parabrachial nuclei) [34,35]. Hippocampal lesions due to
inflammatory but also ischemic, hypoxic, or dysglycemic insults [57,60] may explain long-
term psychological and cognitive disorders observed in survivors of critical illness [25,61].
Interestingly, reduction of oxidative stress in hippocampus is associated with less cognitive
dysfunction in septic rats [52]. There also are arguments for a global brainstem dysfunction
during sepsis. First, a recent study suggested that abolition of cough reflex and oculocephalic
responses in sedated critically ill patients are associated with death and delirium, respectively
[62]. Second, the brainstem nuclei are liable to apoptosis [35] and use of dexmedetomidine,
which have antiapoptotic properties [63], is associated with less delirium in septic patients
[64]. Finally, impaired sympathetic control of heart rate is frequent and associated with
increased mortality in septic patients suggesting a central autonomic regulatory dysfunction
[65].( https://www.scienceopen.com/document/vid/40bc2d61-e843-467b-9f06-
803e361b0977;jsessionid=JtgZWS68ysvIdHJ1KGZsP4qx.master:so-app1-prd?0)

DEMENSIA

Dementia

Multiple neuropathologic processes may underlie dementia, including both

neurodegenerative diseases and vascular disease. Dementia is most common in elderly
individuals, with advancing age being the strongest risk factor. Furthermore, comorbidity (the
presence of more than one disease process) is the rule rather than the exception for dementia
in elderly persons.[1, 2, 3, 4]

Alzheimer Disease

Alzheimer disease (AD) is the most common neurodegenerative disease responsible for
dementia. About half of dementia cases result from AD;[1, 2] however, a variable but
measurable amount of AD pathologic changes exist in most cognitively intact elderly
individuals who undergo autopsy, indicating that AD is a chronic disease with latent and
prodromal stages and suggesting that individuals may have varying abilities to compensate,
either biologically or functionally, for the presence of AD.[5]

As with many neurodegenerative diseases, both rare autosomal-dominant forms of AD and

more common sporadic forms with genetic risk factors without causative mutations exist.
Abnormalities in 3 genes are known to cause AD with high penetrance: APP, PSEN1, and
PSEN2. Autosomal-dominant forms of AD tend to be more severe and occur at a younger age
than sporadic AD but are relatively rare. Sporadic AD accounts for the vast majority of AD
cases. The neuropathologic changes of autosomal-dominant and sporadic AD are largely the
same.

AD is characterized grossly by progressive atrophy and gliosis, first of the hippocampus and
mesial temporal lobe, followed by other association cortices (frontal and parietal lobes), and
finally by primary motor or sensory cortex (occipital lobe).

AD is characterized diagnostically by 2 histologic findings: (1) extracellular amorphus

eosinophilic deposits of amyloid consisting of A peptides (a cleavage product of APP),
which are referred to as amyloid plaques and (2) intraneuronal aggregates of abnormally
modified microtubule-associated protein tau (neurofibrillary tangles; see the image below).

Bielschowsky silver stain of cortex at 400x

magnification demonstrates a neurofibrillary tangle (black arrow) and a neuritic
plaque (white arrow).

Both amyloid plaques and neurofibrillary tangles are readily identified using silver staining
techniques such as Bielschowsky or Gallyas. Amyloid plaques are sometimes referred to as
senile plaques in older literature because of their long association with dementia. Amyloid
plaques with evidence of damaged neuronal processes are called neuritic plaques.[6]
Accumulating evidence suggests that A is involved in the etiology of AD, although the
mechanism has not been fully elucidated. Amyloid angiopathy is another pathologic finding
in the AD spectrum, in which A accumulates in the media of small arteries. Amyloid
angiopathy can be identified using stains for amyloidal protein (Congo red, thioflavin-S), or
immunohistochemical staining against A (see the image below). Although amyloid
angiopathy has been associated with lobar hemorrhages, it is not a strong predictor of
cognitive status.

Congo red stain of a small cortical artery at 400x

magnification demonstrates salmon-colored amyloid deposition in the media of
the vessel.

Current pathologic criteria for the diagnosis of AD require the presence of neuritic plaques;[6]
however, neuritic plaque burden does not correlate well with cognitive status during life.
Instead, neurofibrillary tangle distribution is more strongly associated with cognitive status.

The staging criteria for neurofibrillary tangle distribution has 6 levels (I-VI) referred to as the
Braak stage, with each successive stage demonstrating tangles in additional brain regions.[7]
Neurofibrillary tangles are present in transentorhinal cortex in stage I, in the CA1 sector of
the hippocampus in stage II, in the subiculum in stage III, in other areas of the hippocampus
and the entorhinal cortex in stage IV, in the association cortex in stage V, and in primary
motor or sensory cortex or the granule neurons of dentate fascia in stage VI.[7, 8, 9]

Vascular Dementia

Vascular brain injury (VBI) is widely recognized as a common cause of cognitive impairment
(vascular cognitive impairment) culminating in vascular dementia. Most vascular dementia
cases are sporadic and share risk factors with peripheral vascular disease. A widely used
method for the clinical diagnosis of vascular dementia in life is the Hachinski Ischemic
Score, which is assessed by determining whether the individual has experienced an abrupt
onset or stepwise progressive course of specific signs and symptoms and the presence of
vascular risk factors.[10] Pathologic assessment of VBI has been hindered by the lack of a
clear, standardized, and widely accepted rubric for diagnosis and staging. Gross ischemic
infarcts, lacunar infarcts, arteriolosclerosis, and microscopically identified infarcts (see image
below) have all been independently associated with vascular dementia.
 A. Hematoxylin-eosin-Luxol fast blue staining of basal
ganglia at 100x magnification demonstrates a cavitary infarct. Calcific medial
sclerosis of small arteries is also present. B. At 400x magnification, numerous
foamy macrophages are present within the center of the infarcted tissue.

With the widespread adoption of MRI (beyond its ability to enhance the diagnosis of
ischemic infarcts), more subtle ischemic injury can appreciably be visualized as T2 signal
hyperintensities in white matter in living individuals. Although these changes are often
classified under the rubric of "small-vessel disease," their precise pathologic correlates are
not well understood but may include ischemia-induced demyelination and/or axonal loss,
arteriolosclerosis, microscopic infarcts, breakdown of the blood brain barrier, and/or
breakdown of the blood CSF barrier.

Wharton et al conducted a literature review of studies that utilized samples from the Medical
Research Council Cognitive Function and Ageing Study neuropathology cohort to identify
cerebral white matter lesions. Expression of hypoxia-related molecules and other injury and
protective cellular pathways reported in immunohistochemical and gene expression
microarray studies suggest that hypoxia and ischemia play a role in the pathology of white
matter lesions. Other pathogenic factors include immune activation, blood-brain barrier
dysfunction, altered cell metabolic pathways, and glial cell injury. The investigators reported
that these abnormalities are not confined to white matter lesions but are also found in
apparently normal white matter in brains with lesions, suggesting a field effect of white
matter abnormality within which lesions arise. They concluded that white matter lesions have
a complex pathogenesis that may offer a number of primary and secondary intervention
targets.[11]

Two criteria that have been suggested for the pathologic diagnosis of vascular dementia
include (1) multiple large and/or strategic infarcts in cerebrum[12] or (2) a threshold of 3 or
more microscopic infarcts identified in a systematic screening of cerebral cortex and deep
cerebral structures.[1, 2, 13] VBI is commonly comorbid with AD in elderly patients with
dementia, especially in a community setting.

A rare autosomal-dominant disease that causes multiple small strokes and may culminate in
vascular dementia is cerebral autosomal dominant arteriopathy with subcortical infarcts and
leukoencephalopathy (CADASIL). CADASIL is caused by mutations in NOTCH3.

Lewy Body Disease

Lewy body dementia (LBD) refers to pathologic changes that underlie several closely related
syndromes. Most manifest with a movement disorder component, and the clinical diagnosis
received in life often depends on the interval between the diagnosis of dementia and the onset
of movement disorder symptoms. If a clinical diagnosis of Parkinson disease is followed by
dementia a minimum of 1 year later, then a diagnosis of Parkinson disease dementia is
assigned. If the onset of dementia precedes or is roughly concurrent with the onset of
Parkinson disease, then the clinical diagnosis of dementia with Lewy bodies (not to be
confused with LBD) is used.

By the time the postmortem diagnosis of LBD can be confirmed, years would have passed
since the initial clinical diagnosis, making Parkinson disease dementia and LBD difficult to
distinguish. Most LBDs are sporadic and are frequently associated with increased age and the
male sex. Organophosphate pesticide exposure is a known risk factor. Of interest, several
lines of evidence suggest that a history of cigarette smoking may protect from the processes
that lead to LBD.

Lewy bodies are spherical eosinophilic intraneuronal inclusion bodies surrounded by a clear
halo (see image "A" below). Lewy body distribution and number are the diagnostic findings
of LBD. In pigmented neurons, LBs are easy to identify with standard hematoxylin and
eosinstained sections.

Lewy bodies comprise a number of different aggregated proteins, the most diagnostically
useful of which is alpha-synuclein. Loss of pigment-bearing neurons is seen in the pigmented
nuclei of the brainstem accompanied by the presence of neuromelanin in scavenger
macrophages (pigment "incontinence"). Pigment loss in Parkinson disease is most severe in
the ventrolateral tier of the substantia nigra, which contrasts with normal aging, in which
some pigment loss is seen in the dorsal tier. Immunohistochemical staining against alpha-
synuclein aids in detection of Lewy bodies in nonpigmented neurons such as in cortex (see
image "B" below).

A. Hematoxylin and eosin staining of the substantia

nigra at 400x magnification demonstrates multiple Lewy bodies within a
pigmented neuron. The Lewy bodies are round with a densely eosinophilic core
surrounded by a clear halo. B. Immunohistochemical staining (brown) against
alpha-synuclein at 400x magnification reveals a round Lewy body within the
soma of a neuron.
Distribution of Lewy bodies in the CNS progresses in a rostral manner. Incidental Lewy
bodies present only in the medulla are usually clinically silent or may be associated with
premortem symptoms of autonomic dysfunction. A brain stempredominant distribution of
LB in the medulla and substantia nigra may be clinically silent or associated with a
premortem clinical diagnosis of Parkinson disease. Limbic distribution involves brainstem
structures, as well as the amygdala, entorhinal cortex, and cingulate gyrus. The clinical
correlate for this stage is unclear but may include cognitive impairment.

Diffuse distribution involves all of the brainstem and limbic structures, as well as the
isocortex. In diffuse LBD, the cortex is variably atrophic, and, in more severe cases,
vacuolization of the superficial cortical layers often exists. Most cases of LBD can be
classified using hematoxylin and eosin sections of substantia nigra and immunohistochemical
staining against alpha-synuclein in sections of medulla, amygdala, cingulate gyrus, and
frontal cortex.[14, 15] Pathologic changes of LBD and AD may also coexist in patients with
dementia.

Comorbid Disease

AD, VBI, and LBD are all highly prevalent disease processes and often occur simultaneously.
[1, 2, 3, 4]
Further, clinically silent pathology is very common in the aging population. Over 50%
of all individuals who undergo autopsy and 40% of individuals without dementia have
intermediate or high AD pathology. Approximately 60% of these individuals have chronic
VBI.

In the elderly population, comorbidity is the rule rather than the exception (see the image
below). The likelihood that an individual had clinical dementia preceding death increases
with the number of comorbid pathologies.

Comorbid brain pathologies are common in the

elderly population. This Venn diagram demonstrates the co-occurrence of brain
pathologies as evident from population based autopsy studies of brain aging.

Less-Common Neurodegenerative Dementing Diseases

Frontotemporal dementia
Frontotemporal dementia (FTD) refers to a group of neurodegenerative disorders that are
characterized clinically by early onset (usually sixth and seventh decade), loss of executive
function, and relative sparing of memory function. Pathologically, they have variable atrophy
of the frontal and temporal lobes that is often asymmetric. FTDs are heterogenous with
multiple etiologies and many have characteristic histopathologic changes.[16]

Pick disease is probably the most well-known of the FTDs and is characterized by
widespread presence of spherical intraneuronal Pick bodies that are positive for microtubule-
associated protein tau (MAPT), as well as other proteins (see the image below). Pick bodies
may also be identified using silver staining techniques such as Bielschowsky or Gallyas.

A. Hematoxylin and eosin staining at 400x

magnification of the dentate fascia of the hippocampus reveals round
eosinophilic Pick bodies (arrows) in the soma of granular neurons. B.
Immunohistochemical staining (brown) against tau at 400x magnification reveals
round intraneuronal Pick body in cortical neurons.

One FTD characterized by the presence of ubiquitin-positive inclusions (FTD-U) occurs as

part of a disease spectrum with motor neuron disease. A familial form of FTD, FTD with
parkinsonism linked to chromosome 17, was later found to map to the MAPT locus and has
characteristic tau pathology. Multiple other FTDs exist; some have characteristic neuronal
inclusions (eg, neurofilament, TAR DNA binding protein-43), while others lack distinctive
histopathologic changes. Single gene defects have been identified for many FTDs, including
PGRN, FUS, CHMP2B, and VCP. The prevalence of FTD is low, and the population
prevalence of sporadic and genetic disease is not known.

Prion disease
Prion diseases are a family of neurodegenerative diseases that are unique in 2 ways. First,
they are transmissible although not infectious. Second, the transmitting agent is a misfolded
protein called the prion protein, capable of causing native, normally folded protein to adopt
this disease-associated conformation when introduced into an organism. The transmissibility
of prion diseases was first described in studying an endemic prion disease called kuru among
the Fore tribe of Papua New Guinea. Kuru is characterized by rapid loss of motor and
intellectual function, body tremors, and pathological laughter. Further study revealed that
Fore funeral practice included cannibalism. Since this practice was outlawed among the Fore,
the disease has disappeared.

Creutzfeldt-Jakob disease (CJD) is the most common form of prion disease and occurs at a
rate of approximately one case per one million population per year. Both sporadic and
autosomal-dominant genetic forms of CJD exist. Pathologically, prion diseases are
characterized by spongiform encephalopathy and deposition of highly protease-resistant prion
protein aggregates (see the image below). Spongiform encephalopathythe appearance of
coalescent vacuoles within the grey matter neuropilis accompanied by neuron loss and
gliosis. The vacuoles are dilated neuronal processes. Diagnosis of prion diseases requires
biochemical analyses of the glycosylated forms of the abnormal prion protein.

If a prion disease is suspected by a physician, contacting the National Prion Disease

Pathology Surveillance Center is imperative.

A. Hematoxylin and eosin staining at 400x

magnification of cerebral cortex reveals the coalescent clear vesicles
characteristic of spongiform encephalopathy. B. Immunohistochemical staining
(brown) against protease resistant prion protein reveals the granular
immunoreactivity seen in Creutzfeldt-Jakob disease.

Huntington disease
Huntington disease (HD) is unique among the dementing illnesses in that it is always caused
by a defect in a single gene, HTT. It is almost always autosomal dominant, and, essentially,
no sporadic form exists, although rare de novo mutations exist. HD is caused by a
trinucleotide (CAG) repeat expansion in HTT that causes an elongated polyglutamine repeat
in the Huntington protein. Clinically, HD is primarily characterized by its characteristic
choreiform movement disorder, but it also includes psychiatric disturbances and ultimately
dementia.

Pathologically, HD is characterized primarily by neuronal loss, atrophy, and gliosis of the

caudate and putamen beginning in the anterior medial caudate. As the disease progresses, this
neuronal loss, atrophy and gliosis may involve multiple brain regions. Immunohistochemical
staining against polyglutamine reveals intraneuronal inclusions, although this finding is
usually not necessary for the diagnosis. Pathologic staging is performed by assessing the
amount of atrophy, neuronal loss, and gliosis in the caudate and putamen.[17]

Tauopathies
Tauopathies are a heterogenous group of neurodegenerative disorders that may culminate in
dementia and are characterized by abnormal accumulations of tau protein often both in
neurons and glia (see the image below).[18] This group includes corticobasal ganglionic
degeneration, the Parkinson-dementia complex of Guam (also called Bodig-Lytigo), and
argyrophilic grain disease. Several lines of evidence suggest that AD is also a tauopathy. The
clinical presentation of these diseases varies and includes both cognitive impairment and
movement disorders.
 Immunohistochemical staining (brown) against tau at
400x magnification reveals glial immunoreactivity characteristic of this case of
cortico-basal ganglionic degeneration. (MEDSCAPE)
Dementia (see chapter on Geriatric Psychiatry)

II. Neuropsychiatric consequences of systemic disease

Endocrine Diseases

The patient with hyperthyroidism may have restlessness, over-activity, over-

reactivity, depression and poor concentration. The differential diagnosis
between

thyrotoxicosis and anxiety disorder depends on a history of distinctive symptoms

and on
physical examination. Affective (especiallymanic) and schizophrenic psychosis
has also

been described. With modern treatment, delirium in thyroid crisis has become
rare.

Hypothyroidism may have the following manifestations: mental lethargy, fatigue,

apathy,

irritability, psychomotor slowing and poor memory. Hypothyroidism, occurring in

5% of

patients who are taking lithium carbonate, can be successfully treated with
thyroxine.

Myxoedema patients who are given thyroxine may symptomatically get worse
before they

get better. The bodys readjustment precipitated by the thyroxine intake may
exacerbate

emotional and physical difficulties. The patient with Addisons disease

(hypoadrenalism)

may present with apathy, depression, fatigue, irritability, memory difficulties,

delirium or

dementia. Cushings disease (hyperadrenalism) may manifest as a depressive

illness. The

severity of the depression is not related closely to plasma cortisol

concentrations, and

premorbid personality and stressful life events appear to predispose to the

development of

the affective disorder. Hypopituitarism may present as acute organic reaction, as

coma or as

depression, apathy, lack of initiative and somnolence.

Electrolyte Imbalance

The signs of hyponatremia include fatigue, lassitude, apathy, muscle cramps and

seizures. Water intoxication, a cause of hyponatremia, is sometimes encountered

in patients

with chronic mental illness. It is important to avoid use of carbamazepine in

patients with a

history of compulsive water drinking as the drug may also contribute to

hyponatremia.
Hypokalaemic muscle paralysis may be diagnosed as hysteria, especially in
cases of

familial periodic paralysis in which the hypokalaemia may be triggered by

emotional stress.

Potassium depletion results is lethargy, apathy, anorexia, constipation, anxiety

and

depression.

Renal Disease

Uraemia, particularly with a urea level above 40 mmol, causes an acute organic

reaction in one-third of cases. Other symptoms of uraemia include fatigue,

depression and

somnolence. Chronic uraemic patients showless deep sleep, less rapid-eye-

movement

sleep, and many myoclonic jerks. Sleep is worse the night after a hemodialysis
session,

possibly because of direct effects of the hemodialysis but partly because of

schedule shifts

and other encumbrances of the method. Since depression often occurs in

response to loss

and given that dialysis patients experience many losses (e.g., loss of strength,
energy,

sexual ability, work ability, physical freedom and life expectancy), it is not
surprising that

depression is frequent.

Systemic Lupus Erythematosus (SLE)

The CNS is affected in 50-75% of lupus patients. Neuropsychiatric involvement is

attributed to the manufacture of anti-brain antibodies, which cause a breakdown

in blood-brain barrier and the development of an allergic, autoimmune
encephalitis. Seizures,

disturbances of mental function and consciousness level, and cranial nerve

palsies are

some of the manifestations of cerebral lupus. Schizophrenic or affective

psychosis and
neurotic reactions have also been reported in cases with SLE. The most common
autopsy

findings in the brains of patients with cerebral lupus are microscopic infarcts
and

hemorrhages. Apart from direct involvement of the CNS, other issues worthy of

consideration are the psychological sequelae of the patients awareness of the

illness or its

impact, and the psychiatric side effects of the drugs (e.g., steroids) used to treat
the illness. (www.med.nus.edu.sg/pcm/book/24.pdf)

6. What are the differential between thypoid fever and thypus?

The typhoid germ enters the body through the mouth, usually in contaminated food and
water. Drinking water taken from contaminated wells was a common source of infection.
The patient suffered headache and nose-bleeding, general body aches, a feeling of
tiredness and persistent fever which may have lasted up to three weeks. He developed a
rash, called 'rose spot' and relapsed into delirium and mental confusion. Bronchitis and
pneumonia were secondary and frequently fatal effects.

The typhus germ is transmitted by the bite of the body louse; so the disease was directly
connected with filth and overcrowded unwashed clothes and shared beds. In various
circumstances it was called 'putrid fever', 'ship fever', 'jail fever' and 'camp fever' and was
particularly virulent in cold weather, when poorer people would tend to wear every
ragged stitch they possessed and when their vitality, through lack of warmth and
nourishment, was at its lowest ebb. The symptoms are very similar to those of typhoid:
headache and general pains, chills and fevers, lassitude and delirium. In crowded
conditions typhus could be a real killer. In 1833 P. Gaskell published The Manufacturing
Population of England, and identified common lodging houses as a particular problem:
(http://www.nottingham.ac.uk/manuscriptsandspecialcollections/learning/healthhousing/t
heme3/diseases.aspx)

Typhus - This is caused by the Rickettsia family of bacteria, with Rickettsia

prowazekii causing epidemic typhus and Rickettsia typhi causing murine
typhus. These organisms are spread by human lice and fleas respectively,
after these have fed on an infected individual. The Rickettsia bacteria cannot
live outside of a host cell for long, so in a sense they are an obligate
parasite. Symptoms include a widespread rash, fever, vomiting, photophobia
(unable to look at light) and delusions.

Typhoid Fever - Is cause by the bacterium Salmonella typhi, spread via

water contaminated with the faeces of infected individuals. The symptoms
closely resemble typhus (hence Typhoid which means typhus-like) and last for
about a week, progressing through gradually worsening stages. At the end of
the illness complications like bowel perforations can occur. The fever is the
most prominent symptom, with a plateau at 40 degrees centigrade. One third
 of patients get a rash, but it is not the same as those seen in Typhus
sufferers.

In modern times it is easy to treat with antibiotics, however before these were
discovered it claimed many lives during epidemics. Many historical figures
were affected by both diseases, Anne Frank was a victim of Typhus while she
was imprisoned in a German concentration camp, as were a lot of French
soldiers during the Napoleonic wars. Tsar Nicholas II survived typhoid fever in
1900, as did the painter Georgia O Keefe. Greek war hero Alexander the
Great (on whom a retro-diagnosis has been made) is now thought to have
died of typhoid fever (while his General Hephaestion died of Typhus 8 months
before) rather than the Malaria that was first
suspected. (http://littlemicrobiologyblog.tumblr.com/post/28641064023/the-
difference-between-typhus-and-typhoid)

7. What are the clinical manifestation of Organic Mental Disorder and

thypoid?
ORGANIC MENTAL DISORDER
Gambaran umum gangguan mental organik (Rathus & Nevid, 1991) yaitu :
1. Penurunan fungsi intelektual dan memori
2. Gangguan dalam bahasa (language) dan berbicara (speak)
3. Disorientasi waktu, ruang, dan orang
4. Gangguan motorik
5. Gangguan dalam pembuatan keputusan tindakan
6. Ketidakstabilan perasaan dan emosi
7. Perubahan kepribadian

Gambaran utama dari gangguan mental organik yaitu :

1. Gangguan fungsi kognitif
Meliputi gangguan daya ingat (memory), daya pikir (intelect), daya
belajar (learning)
2. Gangguan sensorium
Misalnya, gangguan kesadaran (consciousness) dan perhatian
(attention)
3. Sindrom dengan manifestasi yang menonjol dalam bidang :
- persepsi (halusinasi)
- isi pikiran (waham/delusi)
- suasana perasaan dan emosi (depresi, gembira, dan cemas) (PPDGJ-III,
1999)

Gambaran klinis Delirium:

1. Gambaran mencolok adanya defisit untuk memusatkan,
mempertahankan, memindahkan perhatian
2. Halusinasi visual sering ditemukan
3. Gangguan irama tidur
4. Fluktuasi kesadarandisorientasi, amnesia, tidak kooperatif.
Gejala-gejala Utama :
1. Kesadaran berkabut
2. Kesulitan mempertahankan atau mengalihkan perhatian
3. Diorientasi
4. Ilusi
5. Halusinasi
6. Perubahan kesadaran yang berfluktuasi
Gejala sering berfluktuasi dalam satu hari, pada banyak kasus, pada
siang hari terjadi perbaikan, sedangkan pada malam hari tampak
sangat terganggu. Siklus tidur-bangun sering terbalik.
Gejala-gejala neurologis:
1. Disfrasia
2. Disartria
3. Tremor
4. Asteriksis pada ensefalopati hepatikum dan uremia
5. Kelainan motorik

Gambaran klinis Demensia:

1. Gangguan Daya Ingat
Gangguan ingatan biasanya merupakan ciri yang awal don menonjol
pada demensia, khususnya pada demensia yang mengenai korteks,
seperti demensia tipe Alzheimer. Pada awal perjalanan demensia,
gangguan daya ingat terjadi secara ringan dan paling jelas untuk
peristiwa yang baru terjadi. Selama perjalanan penyakit demensia,
pasien terganggu dalam orientasi terhadap orang, waktu, maupun
 tempat. Sebagai contoh, pasien dengan demensia mungkin lupa
bagaimana kembali ke ruangannya setelah pergi ke kamar mandi.
Tetapi, pasien tidak menunjukkan gangguan pada tingkat kesadaran.
2. Gangguan Bahasa
Proses demensia dapat mempengaruhi kemampuan berbahasa
pasien. Kesulitan berbahasa ditandai oleh cara berkata yang samar-
samar, stereotipik tidak tepat, atau berputar-putar.
3. Perubahan Kepribadian
Perubahan kepribadian merupakan gambaran yang paling
mengganggu bagi keluarga pasien, hal ini dikarenakan pasien
demensia mempunyai waham paranoid.Gangguan yang terjadi pada
lobus frontal dan temporal dimungkinan menjadi penyebab
perubahan keperibadian pasien. Pasien jadi lebih mudah marah dan
emosinya meledak-ledak. Pasien demensia juga menunjukkan
tertawa atau menangis yang patologis yaitu, emosi yang ekstrim
tanpa penyebab yang terlihat.
4. Psikosis
Diperkirakan 20 -30% pasien demensia tipe Alzheimer mengalami
halusinasi, dan 30-40% mengalami waham, terutama dengan sifat
paranoid.
Diktat PsikiatriGMO dari departemen Psikiatri FK Universitas
Sumatera Utara oleh Syallmsir Bs, Psikiater
http://www.scribd.com/doc/130180396/GANGGUAN-MENTAL-ORGANIK

THYPOID

a. Demam lebih dari 7 hari

Pada kasus tertentu, demam berlangsung selama 3 minggu, bersifat febris remiten dan suhu
tidak seberapa tinggi. Selama minggu pertama, suhu tubuh berangsur-angsur meningkat
setiap hari, biasanya menurun pada pagi hari dan meningkat lagi pada sore dan malam hari.
Dalam minggu kedua, penderita terus berada dalam keadaan demam. Dalam minggu ketiga,
suhu badan berangsur-angsur turun dan normal kembali pada akhir minggu ketiga.

b. Gangguan saluran pencernaan

Pada mulut terdapat nafas berbau tidak sedap, bibir kering dan pecah-pecah (ragaden), lidah
ditutupi selaput putih kotor (coated tongue, lidah tifoid), ujung dan tepinya kemerahan, jarang
disertai tremor. Pada abdomen terjadi splenomegali dan hepatomegali dengan disertai nyeri
tekan. Biasanya didapatkan kondisi konstipasi, kadang diare, mual, muntah, tapi kembung
jarang.

c. Gangguan kesadaran

Umumnya kesadaran penderita menurun walaupun tidak seberapa dalam, yaitu apatis sampai
somnolen. Jarang terjadi sopor, koma atau gelisah.

d. Pada punggung terdapat roseola (bintik kemerahan karena emboli basil dalam kapiler
kulit. Biasanya ditemukan pada minggu pertama demam).

e. Relaps (kambuh) ialah berulangnya gejala penyakit tifus abdominalis, akan tetapi
berlangsung ringan dan lebih singkat. Terjadi pada minggu kedua setelah suhu badan normal
kembali, terjadinya sukar diterangkan. Menurut teori relaps terjadi karena terdapatnya basil
dalam organ-organ yang tidak dapat dimusnahkan baik oleh obat zat anti. Mungkin terjadi
pada waktu penyembuhan tukak, terjadi invasi basil bersamaan dengan pembentukan jaringan
fibrosis. (https://dinkeskebumen.wordpress.com/2013/04/18/mengenal-thypoid-i/)

8. Why the patient complaind screwed talk and agitation?

AGITATION
Agitation is a nonspecific constellation of relatively unrelated behaviors that
can be seen in a number of different clinical conditions, usually presenting a
fluctuating course. Multiple underlying pathophysiologic abnormalities are
mediated by dysregulations of dopaminergic, serotonergic, noradrenergic,
and GABAergic systems. Pathophysiologic mechanisms of agitation that
operate in the different clinical disorders where agitation occurs are
discussed. These pathophysiologic abnormalities are not associated with
distinct clinical features. Although there may be a final common pathway,
there is no unifying etiologic pathophysiology. The author suggests that the
clinician address the underlying pathophysiology through a treatment
intervention that addresses the overarching psychiatric disorder. Generally,
agents that reduce dopaminergic or noradrenergic tone or increase
serotonergic or GABAergic tone will attenuate agitation, often irrespective of
etiology. (http://www.ncbi.nlm.nih.gov/pubmed/11154018)

SCREWED TALK

9. Why he also he has visual hallucination and felt scarry ?

Organic psychosis is suspected when there is a neurological deficit producing
an
altered mental state, which is suggested by altered consciousness, fluctuating
level of
consciousness, memory problems, visual, olfactory, somatic and gustatory
hallucinations
and/or sphincter disturbance. Visual hallucinations, for instance, can be
encountered in the
following conditions: ocular disorders (e.g. macular degeneration, cataracts),
optic nerve
and tract disorders, midbrain lesions (e.g. stroke, tumors), geniculocalcarine
radiation
lesions, occipital or temporal lesions (e.g., stroke, tumours, seizures),
migraine, narcolepsy,
Alzheimers disease, cortical Lewy body disease, Parkinsons disease after
dopaminergic
treatment, drug intoxication or withdrawal, metabolic encephalopathies,
schizophrenia,
depression or mania with mood-congruent hallucinations (Cummings &
Trimble, 1995).
Paranoid symptoms have been mentioned traditionally in Huntingtons
disease and
grandiosity is commonly described in neurosyphilis and sometimes in Picks
disease, due to
predominantly pre-frontal lobe involvement at certain stages of these
illnesses.
Organic mental disorders have known biological causes and
pathophysiological
mechanisms but the boundary between organic and functional disorders
shifts over time,
both within the field of psychiatry and for particular patients. Historically,
mental disorders
(e.g. general paresis of the insane) have been reclassified as organic if a
specific underlying
brain dysfunction could be identified. For an individual patient, a depressive
episode may
turn out to be an early manifestation of an underlying neurological condition
(e.g.
Huntingtons chorea), and the person may be more appropriately diagnosed
to have an
organic mood disorder.
Psychiatric disorders are more likely to develop in vulnerable individuals as a
result
of the interaction between the persons, the stressful situation and the social
and emotional
supports available. To illustrate, the stress ofphysical illness, cognitive
impairments and the
patients premorbid personality may bring about affective changes. Table 1
lists the
neurologic disorders associated with mania or hypomania. Premorbid
personality may
determine a persons reaction to illness and disability while psychosocial
effects may impact
on the nature and severity of anxiety and depression and the ability of patient
to
compensate for his/her cognitive deficits.
10. what are the correlation typhoid fever and organic mental
disorder?

INFECTION LEADING TO MENTAL ILLNESS

In considering an infectious etiology to any chronic mental illness there are at least four
categories to consider. First are those infections already recognized to induce psychiatric
symptoms. These include pneumonia, urinary tract infection, sepsis, malaria, Legionnaire's
disease, syphilis, typhoid, diphtheria, HIV, rheumatic fever and herpes. (Ref: Chuang)

While the psychiatric effects of these infections are known to the medical field, they are
rarely screened for if the initial presentation is made to a mental health professional.
Moreover, the significance of some of these infections may date back to prenatal
development. Research done at the John Hopkins Children's Center and published in the
Archives of General Psychiatry in 2001 found that mothers with evidence of Herpes Simplex
Type 2 infection at the time of pregnancy had children almost six times more likely to later
develop schizophrenia. And in the US, Europe and Japan, birth clusters of individuals who
develop schizophrenia later in life closely mirror the seasonal distribution of Ixodes ticks at
the time of conception (Lyme disease).

Second are those parasitic infections such as neurocysticercosis where the brain is directly
invaded by the infective agent through a well-established, imageable (visible on brain scan)
mechanism (cysts, lesions, cerebral swelling etc.) Signs of psychiatric disease (depression
and psychosis) were found in over 65% of neurocysticercosis cases (caused by a tapeworm
whose incidence in the US is rising due to demographic increases in foreign immigrant
populations.) [Ref: Forlenza] While the mechanisms for psychiatric manifestations are easy
to demonstrate when brain tissue is directly affected, there are also multiple documented
reports in the literature of psychiatric symptoms associated with other parasites like
giardiasis, ascaris (roundworm), trichinae (cause of trichinosis), and Lyme borrelia and
viruses like borna virus. Documentation also exists of these psychiatric symptoms resolving
when the underlying hidden infection is treated.

Dr. J. Packman of Yale University wrote over ten years ago that "Patients with parasitic loads
are more likely to exhibit mental status changes and there is an improvement in mental status
of a subset of psychiatric patients following treatment for parasites." In fact, a review of 1300
human cases of trichinosis in Germany found CNS (central nervous system) involvement in
up to 24% of the cases (Menningeal inflamation or encephalitis). [Ref: Froscher]

Clinically, in cases like neurocysticercosis, the problem is not the lack of a well-defined
mechanism but the lack of mental health practitioners qualified to make such a diagnosis or
even suspect it. Even infectious disease specialists tend to underestimate the scope of the
problem, in part due to underreporting (neurocysticercosis is not a reportable condition in
most states and the incidence of trichinosis is, we believe, vastly underestimated according to
newly developed antibody assays only made available in 2003).
Next are those parasitic, bacterial and viral infections like toxoplasmosis and strep where a
strong statistical link to mental illness has been demonstrated but research is underway to
establish a causal connection. In humans acute infection with toxoplasmosis gondii can cause
brain lesions, changes in personality and symptoms of psychosis including delusions and
auditory hallucinations. Researchers at Rockefeller University and NIMH have suggested that
after streptococcal infection some children may be at increased risk for Obsessive
Compulsive Disorder. Toxoplasma gondii can alter behavior and neurotransmitter function.
Since 1953, eighteen out of nineteen studies of T. gondii antibodies in persons with
schizophrenia and other severe psychiatric disorders have reported a higher percentage of T.
gondii antibodies in the affected persons. (For example, in one large study toxoplasmosis
infection was twice as common in mentally handicapped patients as in healthy controls and in
a recent German study of "individuals with first episode schizophrenia compared to matched
controls, 42% of the former compared to just 11% of the latter had antibodies to
toxoplasma").

Two other studies found that exposure to cats (the primary carrier for toxoplasmosis
transmission) in childhood is a risk factor for the development of schizophrenia. Furthermore,
certain antipsychotic and mood-stabilizer drugs such as Halperidol and Valproic acid
inhibited this parasite in vitro at a concentration below that found in the cerebrospinal fluid
and blood of individuals being treated with this medication, suggesting that some medications
used to treat schizophrenia and bipolar disorder may actually work by inhibiting the
replication of toxoplasmosis gondii. (Ref: Jones-Brando, Torrey, Yolken)

Other studies have shown that antipsychotic drugs like Thorazine, Haldol and Clozapine
inhibit viral replication and that the cerebrospinal fluid of patients with recent-onset
schizophrenia shows a significant increase in reverse transcriptase (an enzyme) activity -
which is an important component of infectious retroviruses (a type of virus). Furthermore,
when the CSF (cerebral spinal fluid) from these patients was used to inoculate a New World
monkey cell line there was a tenfold increase in reverse transcriptase activity which suggests
the presence of a replicating virus. Malhotra has demonstrated the absence of CCR5-32
homozygotes (specific matching genetic codes) in over 200 schizophrenic patients - which
dramatically increases susceptibility to retroviral infection. (Ref: F.Yee).

It is research like this that has led Johns Hopkins virologist Robert Yolken and psychiatry
professor and former special assistant to the Director of the National Institute for Mental
Health Dr. E. Fuller Torrey to believe that toxoplasmosis is one of several infectious agents
that causes most cases of schizophrenia and bipolar disorder. The idea is not new. In fact, as
far back as 1922 the famous psychiatrist Karl Menninger hypothesized that schizophrenia
was "in most instances the byproduct of viral encephalitis." Torrey notes that in the late
nineteenth century schizophrenia and bipolar disorder went from being rare diseases to
relatively common ones at the same time that cat ownership became popular. And Yolken
designed a retrospective study of twenty-five hundred families showing that mothers of
children who later developed psychoses were 4.5 times more likely to have antibodies to
toxoplasmosis than the mothers of healthy controls. Due to the frequency of cat ownership, a
large percentage of the US population (up to 50%) has been exposed to toxoplasmosis but
most immunocompetent carriers remain asymptomatic until another immunological burden
such as HIV or a separate parasite weakens the host defenses and precipitates pathogenic
expression. That is what makes interpretation of the chronic state so tricky and at the
Research Institute for Infectious Mental Illness we make sure to try to identify any parasitic
coinfections before deciding on an appropriate course of treatment.

Finally, while toxoplasmosis gets a lot of attention due to Torrey's and Yolken's pioneering
studies and the known mechanism of brain lesions, there are many other infective agents that
may not target the brain specifically but can severely affect mental function through the
cumulative downstream consequences of chronic infection. While the importance of this link
in the etiopathogenesis of mental illness is rarely recognized, these focal and systemic
infections are very common and their psychiatric effects often severe. (Parasites are the most
common causes of mortality and morbidity in the world.) In this nonspecific category are
scores of parasites, protozoa, helminths, bacteria, fungi and viruses which, if not directly
invading and disabling brain tissue and neurotransmitter function, do so indirectly by
depleting the host of essential nutrients, interfering with enzyme functions, and releasing a
massive load of waste products - enteric poisons and toxins which disrupt brain metabolism.
(A single mature adult tapeworm can lay a million eggs a day and roundworms, which infect
about twenty-five per cent of the world's population, lay 200,000 daily).

Remember, the brain is your body's most energy-intensive organ. It represents only three
percent of your body weight but utilizes twenty-five percent of your body's oxygen, nutrients
and circulating glucose. Therefore any significant metabolic disruptions can impact brain
function first. This link is borne out statistically. Mental patients have much higher rates of
parasitic infection than the general population. Between 1995 and 1996 researchers at the
University of Ancona did stool tests on 238 residents of four Italian psychiatric institutions
and found parasites in 53.8 percent of the residents including all of those residents with
behavioral aberrations(Ref: Giacometti). In our experience parasites are often implicated in
cognitive dysfunction and chronic emotional stress disorders and, to the untrained eye, classic
symptoms like apathy, exhaustion, confusion, appetite and memory loss, "nervous stomach,"
social withdrawal, lethargy and loss of sex drive and motivation are frequently assumed to
signal a depressive disorder without an adequate differential diagnosis being made or even
attempted. Adding to the confusion, classic indicators of acute infection such as fever or
elevated antibodies often reverse themselves in chronic cases due to secondary
hypothyroidism and immunodepression. Unfortunately, until Western psychiatry further
recognizes that the mind/body connection goes in both directions patients will continue to
suffer from a de facto lack of differential diagnostic criteria in clinically identical syndromes.

Even for those clinicians who recognize the devastating psychological effects that chronic
intestinal, focal and even dental infections can have on normal brain function, accurate
diagnosis presents formidable challenges. In fact some standard parasite stool test procedures
identify less than ten percent of active infections and even the "politically correct" holistic
specialty labs miss many infections that are nondetectable in fecal specimens, have
inconsistent shedding patterns, are extra intestinal or otherwise hard to identify. For example,
according to the World Health Organization, over two billion people are infected with worms,
yet rarely will they show up in stool assays.

(These numbers are not surprising once you realize that the exposure vectors are potentially
everything you eat, drink, breathe and touch. If you think you have to leave the country to be
exposed to exotic parasites, think again. In fact, try walking into the kitchen of your favorite
restaurant and see if the cook speaks English.)

At the Research Institute for Infectious Mental Illness we use multiple labs with
complementary strengths and a combination of advanced scientific diagnostic procedures
including O & P microscopy, multifluid antigen and antibody detection, stool cultures,
enzyme immunoassay, mucosal markers, inflammation assays, imaging techniques and other
indirect laboratory indicators combined with extensive historical and clinical evaluations to
identify chronic infectious stressors. (Patients previously diagnosed with "Chronic
Candidiasis" often find that Candida was merely a cofactor or consequence of more
significant infections and infestations which created obstacles to long-term cure.) "Mental"
symptoms often improve dramatically when hidden neuroimmune infections are treated
successfully and normal brain metabolism resumes, especially in "sudden-onset" syndromes.
After identifying and treating the primary infections we focus on rebuilding the host's
immunological defenses and mucosal integrity to prevent relapse. Premature nutritional
supplementation, even in frank anemia, can be counterproductive since some vitamins and
minerals (e.g., iron) can be growth factors for microorganisms which the body intentionally
downregulates the uptake of during active infection. But individually formulated subsequent
nutritional supplementation is usually essential for full recovery. We also screen patients for
heavy metals, environmental chemicals, molds and electromagnetic stressors, "Brain
allergies," food sensitivities, hormone disorders, diet and numerous other variables which can
influence cognitive and affective function. To speed recovery, our evidence-based Integral
Medicine approach may include appropriate treatments from consulting nutritionists,
homeopaths, acupuncturists, herbalists and bodyworkers.

The erosion or loss of brain function is arguably the most frightening and disabling
experience a person can have. Almost by definition, standard psychological or psychiatric
intervention postulates a dichotomy between disorders of the body and those of the mind and
has a long way to go in recognizing the importance of infectious etiologies in mental health
care. The Research Institute for Infectious Mental Illness provides testing, clinical and
consulting services to clients from all over the world and educates professionals in this
critical area. Long distance phone consultations are also available.

This article may be reprinted by anyone if the RIIMI clinic contact info is listed.

11. How to diagnose organic mental disorder?

 PAKE PPDGJ AJA!!! DIBACAIN

12. What is the interpretation the laboratory test showed decreas of

leucocyte and widal test positive? Pemeriksaan penunnjang lainnya
untuk demam thypoid?
 Pemeriksaan penunjang pada klien dengan typhoid adalah pemeriksaan laboratorium,
yang terdiri dari :

a. Pemeriksaan leukosit

Di dalam beberapa literatur dinyatakan bahwa demam typhoid terdapat leukopenia

dan limposistosis relatif tetapi kenyataannya leukopenia tidaklah sering dijumpai. Pada
kebanyakan kasus demam typhoid, jumlah leukosit pada sediaan darah tepi berada pada
batas-batas normal bahkan kadang-kadang terdapat leukosit walaupun tidak ada komplikasi
atau infeksi sekunder. Oleh karena itu pemeriksaan jumlah leukosit tidak berguna untuk
diagnosa demam typhoid.

b. Pemeriksaan SGOT DAN SGPT

SGOT dan SGPT pada demam typhoid seringkali meningkat tetapi dapat kembali
normal setelah sembuhnya typhoid.

c. Biakan darah
 Bila biakan darah positif hal itu menandakan demam typhoid, tetapi bila biakan darah
negatif tidak menutup kemungkinan akan terjadi demam typhoid. Hal ini dikarenakan hasil
biakan darah tergantung dari beberapa faktor :

1) Teknik pemeriksaan Laboratorium

Hasil pemeriksaan satu laboratorium berbeda dengan laboratorium yang lain, hal ini
disebabkan oleh perbedaan teknik dan media biakan yang digunakan. Waktu pengambilan
darah yang baik adalah pada saat demam tinggi yaitu pada saat bakteremia berlangsung.

2) Saat pemeriksaan selama perjalanan Penyakit.

Biakan darah terhadap salmonella thypi terutama positif pada minggu pertama dan
berkurang pada minggu-minggu berikutnya. Pada waktu kambuh biakan darah dapat positif
kembali.

3) Vaksinasi di masa lampau

Vaksinasi terhadap demam typhoid di masa lampau dapat menimbulkan antibodi

dalam darah klien, antibodi ini dapat menekan bakteremia sehingga biakan darah negatif.

4) Pengobatan dengan obat anti mikroba.

Bila klien sebelum pembiakan darah sudah mendapatkan obat anti mikroba
pertumbuhan kuman dalam media biakan terhambat dan hasil biakan mungkin negatif.

d. Uji Widal

Uji widal adalah suatu reaksi aglutinasi antara antigen dan antibodi (aglutinin).
Aglutinin yang spesifik terhadap salmonella thypi terdapat dalam serum klien dengan typhoid
juga terdapat pada orang yang pernah divaksinasikan. Antigen yang digunakan pada uji widal
adalah suspensi salmonella yang sudah dimatikan dan diolah di laboratorium. Tujuan dari uji
widal ini adalah untuk menentukan adanya aglutinin dalam serum klien yang disangka
menderita typhoid. Akibat infeksi oleh salmonella thypi, klien membuat antibodi atau
aglutinin yaitu :

1) Aglutinin O, yang dibuat karena rangsangan antigen O (berasal dari tubuh kuman).

2) Aglutinin H, yang dibuat karena rangsangan antigen H (berasal dari flagel kuman).

3) Aglutinin Vi, yang dibuat karena rangsangan antigen Vi (berasal dari simpai kuman)

Dari ketiga aglutinin tersebut hanya aglutinin O dan H yang ditentukan titernya
untuk diagnosa, makin tinggi titernya makin besar klien menderita typhoid.
 Faktor faktor yang mempengaruhi uji widal :

a. Faktor yang berhubungan dengan klien :

1. Keadaan umum : gizi buruk dapat menghambat pembentukan antibodi.

2. Saat pemeriksaan selama perjalanan penyakit: aglutinin baru dijumpai dalam darah setelah
klien sakit 1 minggu dan mencapai puncaknya pada minggu ke-5 atau ke-6.

3. Penyakit penyakit tertentu : ada beberapa penyakit yang dapat menyertai demam typhoid
yang tidak dapat menimbulkan antibodi seperti agamaglobulinemia, leukemia dan karsinoma
lanjut.

4. Pengobatan dini dengan antibiotika : pengobatan dini dengan obat anti mikroba dapat
menghambat pembentukan antibodi.

5. Obat-obatan imunosupresif atau kortikosteroid : obat-obat tersebut dapat menghambat

terjadinya pembentukan antibodi karena supresi sistem retikuloendotelial.

6. Vaksinasi dengan kotipa atau tipa : seseorang yang divaksinasi dengan kotipa atau tipa, titer
aglutinin O dan H dapat meningkat. Aglutinin O biasanya menghilang setelah 6 bulan sampai
1 tahun, sedangkan titer aglutinin H menurun perlahan-lahan selama 1 atau 2 tahun. Oleh
sebab itu titer aglutinin H pada orang yang pernah divaksinasi kurang mempunyai nilai
diagnostik.

7. Infeksi klien dengan klinis/subklinis oleh salmonella sebelumnya : keadaan ini dapat
mendukung hasil uji widal yang positif, walaupun dengan hasil titer yang rendah.

8. Reaksi anamnesa : keadaan dimana terjadi peningkatan titer aglutinin terhadap salmonella
thypi karena penyakit infeksi dengan demam yang bukan typhoid pada seseorang yang
pernah tertular salmonella di masa lalu.

b. Faktor-faktor Teknis

1. Aglutinasi silang : beberapa spesies salmonella dapat mengandung antigen O dan H yang
sama, sehingga reaksi aglutinasi pada satu spesies dapat menimbulkan reaksi aglutinasi pada
spesies yang lain.

2. Konsentrasi suspensi antigen : konsentrasi ini akan mempengaruhi hasil uji widal.

3. Strain salmonella yang digunakan untuk suspensi antigen : ada penelitian yang berpendapat
bahwa daya aglutinasi suspensi antigen dari strain salmonella setempat lebih baik dari
suspensi dari strain lain.
13. What is the management theraphy for organic mental disorder?
Penatalaksanaan Delirium:
Prinsip terapi pada pasien dengan delirium yaitu mengobati gejala-
gejala klinis yang timbul (medikasi) dan melakukan intervensi personal
danlingkungan terhadap pasien agar timbul fungsi kognitif yang
optimal.Medikasi yang dapat diberikan antara lain :
5. Neuroleptik (haloperidol,risperidone,olanzapine)
Haloperidol (haldol)
Suatu antipsikosis dengan potensi tinggi. Salah satu antipsikosis
efektif untuk delirium.
Risperidone (risperdal)
Antipsikotik golongan terbaru dengan efek ekstrapiramidal lebih
sedikitdibandingkan dengan haldol. Mengikat reseptor dopamine D2
dengan afinitas 20 kali lebih rendah daripada 5-ht2-reseptor.
2. Short acting sedative (lorazepam)
Digunakan untuk delirium yang diakibatkan oleh gejala putus obat
atau alcohol. Tidak digunakan benzodiazepine karena dapat
mendepresi nafas, terutama pada pasien dengan usia tua, pasien
dengan masalah paru.
3. Vitamin, thiamine (thiamilate) dancyanocobalamine
(nascobal, cyomin, crystamine)
Bahwadefisiensi vitamin B6 dan vitamin B12 dapat menyebabkan
delirium maka untuk mencegahnya diberikan preparat vitamin B per
oral.
4. Terapi Cairan dan Nutrisi
Intervensi personal dan lingkungan terhadap pasien delirium
jugasangat berguna untuk membina hubungan yang erat terhadap
pasien dengan lingkungan sekitar untuk dapat berinteraksi serta
dapat mempermudah pasien untuk melakukan ADL (activity of daily
living) sendirinya tanpa tergantung orang lain.

Penatalaksanaan Demensia:
Bantuan yang baik mereka yang membantu pasien berjuang dengan
perasaan bersalah, berduka, marah, dan kelelahan sebagaimana
mereka menyaksian anggota keluarga mereka sendiri menderita.
Pasien yang mendapat dukungan dan psikoterapi edukasional dimana
penyakitnya secara terang dijelaskan. Mereka juga mendapat
 keuntungan dari dukungan yang diberikan oleh keluarganya dalam
menghadapi penyakit yang membuat mereka memiliki disfungsi.
Diktat PsikiatriGMO dari departemen Psikiatri FK Universitas
Sumatera Utara oleh Syallmsir Bs, Psikiater
http://www.scribd.com/doc/130180396/GANGGUAN-MENTAL-ORGANIK

14. What are DD from the scenario?

DELIRIUM BUKAN AKIBAT ALKOHOL DAN ZAT PSIKOAKTIF LAINNYA
- Gangguan kesadaran dan perhatian
o Pdari taraf kesadaran berkabut sampai koma
o Menurunnya kemampuan untuk mengarahkan, memusatkan,
mepertahankan dan mengalihkan perhatian
- Gangguan kognitif secara umum
o Distorsi persepsi, ilusi, halusinasi
o Hendaya daya pikir
o Hendaya daya ingat
o Disorientasi waktu
- Gangguan psikomotor
o Hipo/ hiperaktivitas
- Gangguan siklus tidur-bangun
o Inosomnia
o Gejala memburuk pada malam hari
- Gangguan emosional
o Depresi, anxietas, rasa takut, lekas marah, euforia, apatis, dll.
- Onset hilang timbul kurang dari 6 bulan

F06 GANGGUAN MENTAL LAINNYA AKIBAT KERUSAKAN DAN

DISFUNGSI OTAK DAN PENYAKIT FISIK
Pedoman diagnostik :
- Ada penyakit otak/sistemik yang berhubungan dengan salah satu sindrom
mental
- Adanya hubungan waktu dengan perubahan mental
- Sembuh setelah penyakit yang mendasari sembuh
- Tidak ada bukti yang mengarah pada penyebab alternatif dari sindom
metal ini( sepertri stress atau genetik)

F06.0 HALUSINOSIS ORGANIK

- Kriteria pedoman diagnostik F06

- Adanya halusinasi
- Kesadaran jernih
- Tidak ada penurunan fungsi intelektual
- Tidak ada gangguan afektif yang menonjol
- Tidak ada waham
- Insight masih utuh

(PPDGJ)