THE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
included transient cranial nerve palsies, lower extremity weakness and
paraesthesias, and bowel and bladder incontinence. Multiple previous
investigations had shown only a persistent CSF pleocytosis (Table).
In 1992, the patient had a sub-acute onset of bilateral sensorineural
hearing loss, dizziness when standing, and a sensation of poor balance
hepatosplenomegaly and no visible rash. Cranial nerves were normal
apart from an inferior nasal quadrantanopsia in the right eye (secondary
to the previous hemorrhage) and the bilateral hearing loss. Muscle bulk
was normal, tone was slightly increased in the lower extremities, upper
extremity power was normal, and lower extremity power was
symmetrically decreased: iliopsoas was MRC grade 3/5, hamstrings
were 4-/5, gluteus medius and quadriceps were 4/5, gastrocnemius was
(worse in the dark). She began using a cane and hearing aid. The hearing
loss and balance problems continued to progress slowly. In 1994, she
had acute onset of horizontal diplopia and was found to have a right VI
nerve palsy, which resolved completely within two weeks.
4
+/5, and tibialis anterior and hip adductors were 5/5. Muscle stretch
reflexes were symmetrically brisk in the upper extremities, brisk in the
right lower extremity, the left knee jerk was reduced, the left ankle jerk
was absent, the right plantar response was flexor and the left, extensor.
Coordination was normal. Vibration and joint position sensation were
normal, there was clear loss of pinprick and temperature sensation on the
medial right ankle and the perianal region, and decreased rectal
sensation and tone. She required assistance to stand and walk.
Complete blood count, serum electrolytes, AST, ALT, alkaline
phosphatase, LDH, Ca2+, ESR, ACE, and serum protein electrophoresis
were normal. C-reactive protein (7.9 mg/l, normal < 5) and GGT (69
U/L, normal < 40) were slightly elevated. C-ANCA, rheumatoid factor,
and anti-nuclear antibody were normal. Lumbar puncture revealed an
opening pressure of 12.5, with results similar to previous (Table). CSF
cytology showed morphologically normal lymphocytes. CSF bacterial
and TB cultures, India ink stain, viral PCR (for HSV, CMV, and EBV),
VDRL, and ACE were all negative, and B2-microglobulin was increased
In 1995, she began to be followed by one of the authors (RG). At that
time, her neurological exam was normal, as were serum ACE, HIV
serology, Lyme serology, ANA, VDRL, and CXR. A CT and MRI of her
brain were remarkable only for sinusitis. The sinusitis was asymptomatic
and was not investigated further. (She had been seen by an ENT
specialist on several occasions at the time she began to develop hearing
loss). An initial lumbar puncture (LP) (Table) showed elevated protein,
decreased glucose, and lymphocytosis. This was confirmed on a repeat
LP several days later. The CSF gram stain, bacterial culture, viral
culture, fungal culture, cryptococcal antigen, VDRL, AFB, and p-ANCA
were all negative. The CSF cytology was normal, and oligoclonal bands
were absent. A third LP several months later continued to show
lymphocytosis.
In 1996, she had an acute left lower motor neuron facial palsy. She
received a two week course of oral prednisone, and the facial weakness
resolved completely within three weeks. In 1997, she began to complain
of mild leg weakness that manifested itself principally in difficulty going
up stairs. There was associated decrease in sensation below her
umbilicus, and occasional bowel and bladder incontinence. These new
symptoms were all slowly progressive. In 1998, she had a possible
nocturnal seizure and was started on both oral phenytoin and prednisone,
with some improvement in her balance and no further seizures. In
January 1999, as her prednisone was being tapered, she had acute
worsening of her leg weakness. The prednisone was increased without
improvement, and it was stopped in March 1999. Shortly afterward, she
fractured her right hip after slipping in the bath. She recovered well and
was stable until December when she was admitted to hospital with fever
and worsened left leg weakness. She was treated with IV steroids and
returned to her previous level of weakness within days.
(
6.54 mg/L, normal approx. < 1.2 mg/L). EMG and nerve conduction
studies were consistent with multiple radiculopathies in both upper and
lower extremities. An MRI of the brain and spinal cord showed
gadolinium enhancement of multiple cranial nerves, the basal meninges,
the spinal meninges and roots, and areas of the spinal cord (Figures 1-3).
CXR, CT scan of the chest, ultrasound of the abdomen and pelvis, and
gallium scan did not reveal disease outside of the nervous system. A PPD
skin test was negative. A biopsy of dorsal lumbar nerve roots revealed
noncaseating granulomas infiltrating the nerves (Figure 4). A diagnosis
of neurosarcoidosis was made.
Treatment was begun with oral imuran and intravenous
methylprednisolone (1 gram twice per week), and the patient returned
home. Three months later (June 2000), after receiving in-patient
physiotherapy five days per week for the previous month, she and her
husband both felt she had improved. She could walk well with a walker,
and take four or five steps without it. She no longer needed laxatives and
was performing intermittent bladder catheterization. She felt her
sensation was improved. On neurological exam she had improved her
lower extremity power by one MRC grade (e.g. 4- to 4) in each of the
weak muscles. Her reflexes were unchanged. She continued on the same
treatment, and three months later (September 2000) her power had again
improved by one grade and she could climb stairs using hand rails. Her
weekly dose of methylprednisolone was gradually decreased to 250mg
per week, but she complained of burning pains in her left arm and leg
that resolved when the dose was increased to 500mg. When seen
recently (February 2001) she reported improved sensation on her trunk,
a return of bladder sensation and slowly improving mobility.
Further investigations performed included another LP (in 1997, again
showing negative cultures and AFB), a gallium scan in 1997, a
myelogram in 1999, an MRI of the spine with gadolinium (T11 to S1) in
January 2000, and an EMG with nerve conduction studies. All were
normal.
At admission, she complained of severe leg weakness requiring a
walker, decreased leg and sacral sensation, and complete lack of bowel
and bladder control. Medications included phenytoin, maalox, colace,
and ativan. Her past medical history included a hysterectomy, recurrent
urinary tract infections, ocular laser treatment for a retinal hemorrhage
due to a “blocked vein”, and migraine headaches treated with naprosyn.
There was no significant family history.
General physical examination was unremarkable, with no
Table: Lumbar Puncture Results
Date
RBC Count (/µl)
WBC Count (/µl)
Mono-Nuclear cells (%)
Protein (g/L)
1.81
Glucose (mmol/L)
May 16 1995
May 19 1995
August 10 1995
July 15 1997
February 2000
4
414
65
22
0
110
12
66
27
22
100
100
100
100
91
2.3
2.4
2.4
2.4
1.9
1.67
1.51
1.33
2.44
3
50