Neurology Writeup #2 09/02/2018

Bo Guan KCH/Downstate

CC: Patient is a 70 year African American male who was brought in by family member for slurred speech
and progressive weakness to the right side.
HPI: Patient is a 70-year-old African American male, with a past medical history of diabetes, hypertension,
prostate disease and prostatectomy, brought to the ED by family for slurred speech and progressive
weakness over the past week. Per patient’s daughter, patient came from Guyana five days for a three month
stay. Over the past 3 weeks the patient has been exhibiting slurred speech to his daughter over the phone,
however he did not see any doctors in Guyana over that time. When he arrived, his daughter also noticed
him dragging his right foot while ambulating. Per the daughter, he has not been at baseline since July.
They deny loss of consciousness or seizure activity. Patient denies dizziness, headache, chest pain, fever,
chills, and change in appetite, weight loss, or blood in stool or urine. He has been on aspirin for the past 5
days.
PMH: Diabetes, hypertension, prostate disease, prostatectomy
Medication: Lorazepam 2mg PRN, amlodipine 2.5mg/day, aspirin 81mg/day, atenolol 2.5mg/day,
enalapril 10mg/day, gabapentin 100mg t.i.d
Allergy: NKDA
Family History: Non-contributory
Social History: Patient denies tobacco, alcohol, or drug use.
_____________________________________________________________________________________

General physical examination:

The patient is well-appearing. There is no tenderness over the scalp or neck and no bruits at the neck.
There is no proptosis, lid swelling, conjunctival injection, or chemosis. Cardiac exam shows a regular rate
and no murmur. There is generalized atrophy

Neurological Exam:

Mental status:
Patient knows that he is in the hospital but does not know which one. He is disoriented to time, follows 2
steps commands, not able to state days of week forward or backwards, and not able to calculated quarters
in $1.75.
Language:
Impaired repetition, mild global aphasia, not able to write a whole sentence
Cranial nerves:
CN II: Visual fields are full. Pupils are 3 mm and briskly reactive to light. (3mm to 2mm)
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Bo Guan KCH/Downstate

CN III, IV, VI: Normal smooth pursuit following the finger making the H pattern. Normal convergence.
No nystagmus.

CN V: Facial sensation is intact to pinprick in all 3 divisions bilaterally. Jaw movement intact.

CN VII: Face is symmetric with normal forehead wrinkle, eye closure and smile.

CN VIII: Finger rub intact, bilateral

CN IX, X: Palate elevates symmetrically. Swallow is intact.

CN XI: Head turning and shoulder shrug are intact

CN XII: Tongue is midline with normal movements and no atrophy.

Motor:
Right arm pronator drift, low tone in all four extremities .5/5 strength in left upper and lower extremities,
4+/5 right upper extremity, right lower extremity 5/5 except right ankle flexion 4+/5. (muscle strength
exam is not accurate due to lack of cooperation)

Reflexes:
Reflexes are 3+ and symmetric at the biceps, triceps, knees, and ankles. Plantar responses are flexor.
Sensory:
Light touch, pinprick, position sense, and vibration sense are intact in fingers and toes.
Coordination:
Dysmetria of finger to nose on right, heel to shin intact; rapid finger tapping slow on right. Intention
tremor during finger to nose test.
Gait/Stance:
Able to do heel and toe walking but unsteady tandem gait.
Neurology Writeup #2 09/02/2018
Bo Guan KCH/Downstate

Laboratory Data:

Complete Metabolic Panel:

Diagnosis: Other speech disturbances ()

Na (mmol/L): 139 (reference range: 136 - 146)
K (mmol/L): 5.6 (reference range: 3.5 - 5.0)
Cl (mmol/L): 105 (reference range: 98 - 106)
CO2 (mmol/L): 21 (reference range: 24 - 31)
Anion Gap: 13
BUN (mg/dL): 16 (reference range: 8 - 23)
Creat (mg/dL): 1.06 (reference range: 0.70 - 1.20)
BUN/Creat
15.1
Ratio:

Gluc (mg/dL): Random Glucose (normal) 70-99 mg/dL

187 (reference
Fasting Glucose (normal) 70-99 mg/dL
range: 70 - 99)
Impaired Fasting Glucose 100-126 mg/dL
Ca (mg/dL): 9.36 (reference range: 8.8 - 10.2)
T Prot (g/dL): 6.5 (reference range: 6.0 - 8.5)
Albumin
3.8 (reference range: 3.3 - 6.1)
(g/dL):
AST (U/L): 12 (reference range: 10 - 50)
ALT (U/L): 14 (reference range: 0 - 41)
Alk Phos (U/L): 59 (reference range: 35 - 145)
T. Bili (mg/dL):0.17 (reference range: 0.0 - 1.2)
Indices (H):Slightly Hemolyzed
:
male
Calculated (estimated) glomerular filtration rate (eGFR) may not be valid for
GFR patients of extreme body size (obesity, malnutrition, amputees, muscle
Disclaimer: wasting) or with unusual dietary intake (vegetarian, creatine supplements).
The formula has not been validated in the elderly and other ethnic groups.
GFRMAA (mL
>=60
/min /1.73m):
GFRMNAA
(mL /min >=60
/1.73m):
IID: 701-2A
Neurology Writeup #2 09/02/2018
Bo Guan KCH/Downstate

CBC:

WBC (/nL):8.29
RBC (/pL):5.21
HGB (g/dL):15.2
HCT (%):46.1
MCV (fL):88.5
MCH (pg):29.2
MCHC (g/dL):33.0
RDW (%):13.4
PLT (/nL):197
MPV (fL):11.3
NRBC (/nL):0.00

Imaging:

1. Large, probable extra-axial left frontal parietal mass 5.8 x 8.2 x 3 cm (CC x AP x transverse) with
aggressive features including adjacent osseous and scalp invasion

2. Significant mass effect with 1.2 cm left right midline shift with partial effacement of the left lateral
and third ventricle without ventricular treatment at this time. Mildly medialized left uncus without frank
transtentorial herniation.
_____________________________________________________________________________________

Assessment:

In summary, patient is a 70yo man with past medical history of hypertension, and diabetes mellitus who
presented to ED for slurred speech, word-finding difficulties and right side weakness for a few weeks.
Exam showed mild global aphasia and slurred speech and right side weakness. CTH showed large,
probable extra-axial left frontal parietal mass with vasogenic edema and midline shift.

#Left sided brain mass likely 2/2 meningioma vs malignant

-Circular mass in peripheral cortex on the CT scan likely representing meningioma

-Neurosurgery consulted, follow up recs

Neurology Writeup #2 09/02/2018
Bo Guan KCH/Downstate

-dexamethasone 10mg iv stat given, consider continuing per neurosurgery recs -f/u malignancy w/u:
CT chest, abdomen and pelvis w w/o contrast -f/u brain MRI brain w w/o contrast

-Continue NS 50 cc/hr as patient is receiving contrast

Differential Diagnosis
•Acute Subdural Hematoma in the ED
•Encephalitis
•Epidural Hematoma in Emergency Medicine
•Hemorrhagic Stroke
•Ischemic Stroke

Workup:

Patients with brain cancer are predisposed to medical complications, including bleeding disturbances
(hyperviscosity), metabolic disorders (hypercalcemia), and production of excessive hormones (syndrome
of inappropriate antidiuretic hormone secretion).

• Complete blood cell count (CBC)

• Coagulation studies

• Electrolyte levels

• Comprehensive metabolic panel

Plan:

Problem 1. Focal seizure

The patient should continue her current anti convulsive medications. Even though the EEG is negative,
she can still be having electrogenic seizures that are simply not detected due to EEG limitation. She
should follow up with neurology outpatient and also the epilepsy clinic if her episodes continue.

Problem 2. Headache
The patient should continue with her gabapentin medication. Surgery is not indicated because the neck
MRI is negative. The patient should follow up with outpatient pain management for further assessment.
Problem 3. Sjogren Syndrome.
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Bo Guan KCH/Downstate

Continue follow up with rheumatology outpatient clinic.

Problem 4. Hypertension.
Continue current medications. Monitor blood pressure daily.

Discussion
Management of vasogenic edema in patients with primary and metastatic brain tumors
INTRODUCTION — The vasogenic edema that surrounds many brain tumors contributes significantly to
morbidity. This edema results from disruption of the blood-brain barrier, allowing protein-rich fluid to
accumulate in the extracellular space.
PATHOGENESIS — Tumor-related disruption in the blood-brain barrier is caused by two major
mechanisms:
●The local production of factors that increase the permeability of tumor vessels such as vascular
endothelial growth factor (VEGF) [2], glutamate [3], and leukotrienes [4].
●The absence of tight endothelial cell junctions in tumor blood vessels. These vessels develop in response
to angiogenic factors such as VEGF [2] and basic fibroblast growth factor (bFGF, FGF2) [5].
In large part, VEGF is responsible for the loss of integrity of the blood-brain barrier in brain tumors.
Gliomas, meningiomas, and metastatic tumors all have upregulation of VEGF [6-9]. VEGF is secreted by
tumor cells as well as host stromal cells and binds to its receptors VEGFR1 and VEGFR2, which are
located primarily on the surface of endothelial cells. VEGF stimulates the formation of gaps in the
endothelium, a process that leads to fluid leakage into the brain parenchyma, thereby resulting in
vasogenic edema [10,11]. Another possible mechanism is mass effect of the tumor on the veins of the
brain, causing increased capillary permeability.
Vasogenic edema tends to spread more readily in the extracellular space of white matter rather than gray
matter, possibly because of lower resistance to flow within the white matter [12]. Tumor-related edema
may disrupt synaptic transmission, alter neuronal excitability, and contribute to headaches, seizures, focal
neurologic deficits, and encephalopathy. Furthermore, unchecked cerebral edema may result in fatal
herniation because the brain is encased in the rigid cranium.
GLUCOCORTICOIDS — Most patients with brain tumors and peritumoral edema can be adequately
managed with glucocorticoids. Reduction of intracranial pressure (ICP) and improvement in neurologic
symptoms usually begin within hours [13]. A decrease in capillary can be identified within six hours [14],
and changes of diffusion-weighted magnetic resonance imaging (MRI) indicating decreased edema are
identifiable within 48 to 72 hours [15]. However, adequate reduction in elevated ICP resulting from
peritumoral edema may take several days with glucocorticoid therapy alone, and additional treatment may
be required in the initial management of these patients
The mechanism of action of glucocorticoids for control of vasogenic edema is not fully understood.
Dexamethasone upregulates Ang-1, a strong BBB-stabilizing factor, and it downregulates vascular
endothelial growth factor (VEGF), a strong permeabilizing factor, in astrocytes and pericytes .
Glucocorticoids may also increase the clearance of peritumoral edema by facilitating the transport of fluid
into the ventricular system, from which it is cleared by cerebrospinal fluid (CSF) bulk flow [20].
Neurology Writeup #2 09/02/2018
Bo Guan KCH/Downstate

In patients with severe symptoms, the usual initial dexamethasone regimen consists of a 10 mg loading
dose, followed by 4 mg four times per day. For most patients, however, smaller total daily doses (4 to 8
mg per day) are adequate and less toxic [21]. A total maintenance dose of 16 mg per day is typically
reserved for patients with significant edema and deficits.
Although it has been customary to administer dexamethasone in four divided daily doses, its biologic
half-life is sufficiently long (36 to 54 hours) to allow once- or twice-daily dosing, and this approach is
often used for maintenance therapy [22]. To minimize complications, subsequent dosing should be
modified to use the lowest possible dose necessary to control peritumoral edema. (See 'Complications'
below.)
Most patients begin to improve symptomatically within hours and achieve a maximum benefit from a
given dose of glucocorticoids within 24 to 72 hours, although standard neuroimaging studies may not
reveal decreased edema for at least a week [22]. In general, headaches tend to respond better than focal
deficits. If a dexamethasone dose of 16 mg per day is insufficient, the dose may be increased further [24].
Once patients have responded, glucocorticoids should be gradually withdrawn, if possible [25]. Because
dexamethasone, the most commonly used glucocorticoid for brain edema, has a long duration of action,
the drug should be tapered approximately every four days. For patients in good clinical condition, this
may entail a reduction in dose of up to 50 percent every four days. However, for those not tolerating
glucocorticoid withdrawal, a more protracted course and chronic treatment may be required.
Glucocorticoids can change the appearance of brain tumors on MRI and therefore affect the interpretation
of imaging results. In one study, glucocorticoids decreased the size of the contrast-enhancing tumor and
surrounding edema in 90 percent of malignant glioma patients within two weeks of treatment [27].
Another MRI study of glioblastoma patients revealed significant changes in permeability parameters in
the contrast-enhancing tumor 48 to 72 hours after dexamethasone administration [28]. For these reasons,
tumor response assessment should be done cautiously in patients whose glucocorticoid dose has changed
in between scans [29]. Most clinical trial protocols require patients to be on a stable dose of
glucocorticoids for at least five days before the baseline MRI. (See "Assessment of disease status and
surveillance after treatment in patients with primary brain tumors".)
Despite the beneficial effect of glucocorticoids, they are associated with a large number of well-known
side effects (table 1) (see "Major side effects of systemic glucocorticoids"). The frequency of these
complications can be reduced by using the lowest possible dose [22]. Common side effects include
insomnia, essential tremor, and hiccups; patients should be warned in advance that they may occur. Three
complications are of particular concern to patients with brain tumors: gastrointestinal complications,
steroid myopathy, and opportunistic infections such as Pneumocystis pneumonia (PCP). In addition,
retrospective studies have suggested that use of steroids may be associated with decreased overall survival
in patients with glioblastoma, independent of potential confounding factors such as tumor size and
performance status [30].
Glucocorticoid-induced myopathy contributes significantly to morbidity in patients with brain tumors.
Myopathy is a common complication, with an estimated incidence between 2 and 20 percent. The risk of
developing steroid myopathy appears to be significantly lower in patients taking phenytoin, possibly due
to induction of hepatic metabolism of dexamethasone by phenytoin. (See "Glucocorticoid-induced
myopathy".)
Neurology Writeup #2 09/02/2018
Bo Guan KCH/Downstate

The majority of patients develop proximal weakness between the ninth and twelfth weeks of
glucocorticoid treatment, although there is marked variation in individual susceptibility. Some patients
become weak after a low dose of glucocorticoids for a few weeks, while others never develop myopathy
despite receiving large doses of glucocorticoids for months or years. The onset is usually subacute,
occurring over several weeks. Muscle pain is not a feature and tendon reflexes are preserved.
Pneumocystis pneumonia — PCP is a life-threatening opportunistic infection that occurs in
immunocompromised hosts, including patients with brain tumors treated with glucocorticoids. (See
"Pulmonary infections in immunocompromised patients" and "Epidemiology, clinical manifestations, and
diagnosis of Pneumocystis pneumonia in HIV-uninfected patients".)

The risk of symptomatic PCP infection is increased while glucocorticoids are being tapered [31,32].
Concurrent chemotherapy may be an additional risk factor for the development of PCP [33]. In a
retrospective review of 587 patients with primary brain tumors seen at a single institution over an eight-
year period, there were 11 histologically documented cases of PCP in 10 patients (1.7 percent) [34]. The
patients had been on dexamethasone for a median duration of three months when symptoms first
developed. In 8 of 11 episodes, PCP occurred during the steroid taper.

The mechanism by which glucocorticoids predispose to the development of PCP is poorly understood, but
suppression of cellular immunity leading to reactivation of latent infection probably plays a role. Why
PCP more commonly develops during steroid taper is also unknown. Possible factors include increased
immune-mediated lung damage from PCP infection, which had been suppressed by higher doses of
glucocorticoids, and a positive effect of glucocorticoids on surfactant phospholipids that are decreased in
PCP [35].

A significant increase in intracranial pressure (ICP) can be a medical emergency, and treatment should be
undertaken as expeditiously as possible. Although glucocorticoids are an important component of therapy,
additional interventions during the first 24 to 72 hours may be required. These approaches are discussed
elsewhere. (See "Evaluation and management of elevated intracranial pressure in adults", section on
'General management' and "Evaluation and management of elevated intracranial pressure in adults",
section on 'Specific therapies'.)

Symptoms not caused by recurrence of brain edema may develop during the course of the steroid taper
(steroid withdrawal syndrome). These include headache and lethargy that may mimic recurrence of brain
edema as well as myalgias and arthralgias (steroid pseudorheumatism). All of the symptoms respond to
raising the dose slightly and tapering more slowly.

SYMPTOMATIC PLATEAU WAVES — Plateau waves are sustained pressure waves that normally
occur within the brain and are caused by activities that transiently raise the intracranial pressure (ICP; eg,
standing, sneezing, coughing). In the presence of a brain tumor, significant further increases in ICP can
temporarily cut off cerebral perfusion, leading to loss of consciousness. Although the treatment of choice
for such cases is glucocorticoids and acute neurosurgical intervention, patients with steroid-refractory
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symptomatic plateau waves may benefit from the addition of acetazolamide [36]. (See "Evaluation and
management of elevated intracranial pressure in adults", section on 'Waveform analysis'.)

NOVEL TREATMENTS — As a result of the complications of glucocorticoid therapy, there is interest in

alternate treatments for peritumoral edema.

Since vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of
peritumoral edema, anti-VEGF monoclonal antibodies such as bevacizumab or inhibitors of VEGF
receptors are useful in reducing edema [37,38]. The steroid-sparing effects of bevacizumab were
demonstrated in a randomized phase II study of bevacizumab with or without irinotecan in patients with
recurrent glioblastoma, in which 30 to 50 percent of patients had a sustained reduction in glucocorticoid
dose and approximately 20 percent achieved a complete taper [39]. (See "Management of recurrent high-
grade gliomas", section on 'Bevacizumab'.)

Corticotrophin-releasing factor reduces peritumoral edema by a direct effect on blood vessels independent
of the release of adrenal glucocorticoids and has been effective in animal models [40-42].

In a placebo-controlled phase III trial of corticorelin acetate, a synthetic peptide of corticotropin-releasing

factor, the primary endpoint of 50 percent reduction in dexamethasone and improvement in performance
scores was not reached. The study, however, demonstrated a strong trend in favor of corticorelin acetate
leading to statistically significant reductions in steroid-related adverse events of myopathy and
Cushingoid features [43].

A preclinical study suggested that cyclooxygenase-2 (COX-2) inhibitors may be effective in treating
cerebral edema [44], but larger clinical studies have not been conducted.

section on 'Specific therapies'.)