This document discusses several topics related to immunology of the nervous system, including: - A case study of a 14-year-old boy who developed Guillain-Barré syndrome after an influenza infection. He was treated with IVIG and recovered fully in 14 days. - A case of an 8-year-old boy with chronic inflammatory peripheral neuropathy who was treated with IVIG, steroids, and achieved sustained improvement by receiving IVIG every 3 weeks. - A 38-year-old woman presenting with symptoms suggestive of multiple sclerosis, where CSF analysis found oligoclonal bands confirming the diagnosis of MS.

1. Immunology
Of The
Nervous
System

2. Nervous System Immunology
•General
• Immunology of CNS
• Immunology of
Peripheral Nervous
System

60. Case : Guillain-Barré syndrome
A 14-year-old boy awoke one morning 2 weeks after an episode of
influenza with a mild weakness in his legs; his sceptical parents
wondered if this was a ploy to avoid school but during the day he
developed pain in his back and 'pins and needles' in his feet. He was
considerably worse the next day and complained of weakness in his arms
as well, and by the evening he was unable to stand and was admitted to
the hospital with suspected acute idiopathic inflammatory
polyneuropathy. Lumbar puncture showed no cells but a slightly raised
protein level in the CSF. Peripheral nerve conduction studies the next day
revealed demyelination, confirming a diagnosis of Guillain-Barré
syndrome. There was concern when he developed autonomic
dysfunction, with bladder atony and ileus that evening, and he was
treated with high-dose intravenous immunoglobulin (1g/kg body weight
for each of 2 days); he made a complete recovery in 14 days. Antibodies
to ganglioside GD1 were subsequently shown in the pretreatment serum
sample.

61. Chronic inflammatory peripheral neuropathy
An 8-year-old boy presented with gradually increasing weakness in his
arms. Leg weakness followed after 2 weeks and he experienced steady
but slow downhill progression over 4 weeks. He had no consistent
sensory symptoms. On examination he was found to have a motor
tetraparesis, predominantly in the arms. Sensation was normal. Nerve
conduction studies showed a demyelinating motor neuropathy in upper
and lower limbs, with motor conduction velocities of 26m/s. Antibodies
to GM1 ganglioside were present in the serum, confirming the diagnosis
of chronic multifocal motor neuropathy. He was treated initially with
prednisolone but this provoked further deterioration.
Intravenous immunoglobulin (IVIG) (2g/kg body weight) was initially
instituted every 8 weeks, with an initial excellent response after 5 days
which gradually deteriorated after 4 weeks, returning to pretreatment
levels by 8 weeks. This response to therapy was confirmed by a further
infusion, after which changing the interval between infusions to 3 weeks
and infusing IVIG (at a dose of 0.8g/kg) resulted in sustained
improvement.

62. Case Multiple sclerosis I
A 38-year-old woman presented with tingling, numbness and clumsiness of
both hands for 1 week, with a band of numbness from the umbilicus to the
axillae. Six months earlier, following an upper respiratory tract infection, she
had experienced paraesthiae in the feet, numbness from the waist downwards
and 'burning' pains behind the right ear. She was anxious because her maternal
grandmother had suffered from multiple sclerosis.
On neurological examination, she had absent abdominal reflexes with brisk
tendon jerks and bilateral extensor plantar responses. Blood investigations were
normal, including haemoglobin, white-cell count and differential, erythrocyte
sedimentation rate, vitamin B12 and folate levels and syphilis serology. A
lumbar puncture was carried out. The cerebrospinal fluid (CSF) investigation
results are shown in Table C17.1. Oligoclonal IgG bands (see Fig. 19.8) are not
found in normal CSF, but are found in 90% of patients with multiple sclerosis;
in the absence of clinical signs of infection, this test is almost diagnostic of
multiple sclerosis (see Table 17.3).
The likely clinical diagnosis was multiple sclerosis; other possible diagnoses,
such as neurosyphilis or subacute combined degeneration of the cord, were
excluded by the above investigations.

63. Protein concentration 0.4g/l (NR 0-0.4g/l)
Red blood cells None
Lymphocytes 3 x 106/l (NR <5 x 106/l)
IgG concentration 123mg/l (NR <60mg/l)
Albumin concentration 470mg/l (NR <400mg/l)
IgG/albumin ratio 26% (NR 4-22%)
IgG index 1.07 (NR <0.7)
Isoelectric focusing Oligoclonal bands present
Table Cerebrospinal fluid investigations

64. here is no specific treatment which will reverse demyelination, although
each episode is usually associated with some recovery as the initial
oedema subsides. Corticosteroids have been used in an acute attack to
suppress the inflammatory response, with intravenous methyl-
prednisolone being used in moderate to severe relapses. Interferon-beta
has been shown to have some effect in relapsing/remitting disease in
placebo-controlled trials; patients were monitored for up to 5 years with
enhanced nuclear magnetic imaging and those on higher doses of
interferon-beta had a somewhat reduced rate of new lesions. Such
treatment was well tolerated but many questions remain; the very high
costs of the therapy and the relatively small benefit to an individual
patient means that currently therapy is limited. Immunosuppressive
drugs, such as azathioprine and cyclosporin, are unhelpful, probably due
to poor penetration of the blood-brain barrier. Trials of immune
stimulation have been disappointing and interferon-gamma made the
disease worse.
Multiple sclerosis III

65. Case Myasthenia gravis
A 67-year-old man, complaining of double vision, was found to
have bilateral ptosis, covering most of the pupil on the right side
and partially obscuring that on the left. The ptosis was worse in the
evening and almost absent in the morning. He admitted to tiredness
in the arms and legs on exercise, which recovered with resting. A
clinical diagnosis of ocular myasthenia gravis was made. His
Tensilon test was positive but electromyography was inconclusive.
His serum contained antibodies to thyroid microsomes (positive at
1/1600) and to acetylcholine receptors (see Section 19.7). The
patient improved on treatment with pyridostigmine.
This case is not typical of myasthenia gravis but demonstrates that
myasthenia may affect mainly ocular muscles (although only 60%
have detectable antibodies to acetylcholine receptors of skeletal
muscle). Myasthenia gravis is more commonly a disease of young
women, who present with increasing systemic muscle fatigue.