Guillain–Barré syndrome A rare manifestation of Hansen’s ds disease

Neurology India
Official Publication of the Neurological Society of India
January-February 2017 / Vol 65 / Issue 1
ISSN 0028-3886
www.neurologyindia.com

Letters to Editor
Guillain–Barré syndrome: A rare manifestation of
Hansen’s disease
Sir,
Guillain–Barré (GB) syndrome was described by the French
neurologists Guillain, Barre, and Strohl. It is an acute
autoimmune polyradiculopathy that is characterized by
progressive symmetrical muscle weakness. [1] The patients
develop acute paralysis with areflexia. It is often preceded by
infections such as Campylobacter jejuni, Mycoplasma pneumonia,
Hemophilus influenza, cytomegalovirus, and Epstein‐Barr virus
infections by at least 3 weeks. We report a case of a 45‐year‐old
gentleman presenting with leprosy as a rare cause of GB
syndrome.
The patient presented to the hospital with complaints of
weakness affecting all 4 limbs since the last 5 days. The
weakness was distal as well as proximal. The patient also
turned out to be a case of Hansen’s disease. This was
detected approximately 2 months before his presentation
to the hospital as a result of ulceration of the foot. He was
off treatment because of gastric ulcerations. There was no
other significant medical history. The patient presented
with normal higher mental functions and was found to have
a power of 2 of 5 proximally and 3 of 5 distally. There was
generalized areflexia with bilateral flexor plantar response.
The sensory loss was restricted to anesthetic patches on the
back and few patches on the trunk. The patient had palpable
nerves—bilateral radial and ulnar nerves. The foot lesions
had healed in the left foot; however, they persisted in the
right foot.
The patient was evaluated for nerve conduction velocity (NCV),
which was suggestive of GB syndrome. He was taken up for
sural nerve biopsy which showed features that were suggestive
of Hansen’s disease. The slides were reviewed at 2 teaching
institutes and yielded consistent results. Other investigations
and possible causes of neuropathy (malarial parasite, hepatitis
B surface antigen, human immunodeficiency virus (HIV),
rheumatoid arthritis factor, antinuclear antibody, C3, elevated
sugars, and thyroid levels) were negative.
The patient was deteriorating rapidly, and therefore, a course
of intravenous immunoglobulins (IvIg) was initiated. Dapsone
was also initiated. After therapy with IvIg, the patient improved
rapidly.
GB syndrome is a neuropathic condition that is characterized
primarily by progressive symmetrical weakness and areflexia.
Symptoms usually peak at 4 weeks. [1] Several infections
affecting predominantly the respiratory and the gastrointestinal
tract are implicated in the development of this syndrome. [1,2]
While not commonly implicated, vaccination is rarely known to
be associated with the syndrome. Influenza, swine flu, tetanus,
hepatitis, and more recently, influenza A vaccination are few
of the examples that may cause the syndrome. [1,2]
Some of the differential diagnosis of the syndrome include
brainstem involvement, spinal cord affliction, muscle and
neuromuscular disorders, and polyneuropathies such as
chronic inflammatory demyelinating polyneuropathy. The
latter is acquired symmetrical, proximal and distal limb
weakness and sensory disturbances progressing over 2 months.
It is also known to be caused by infective agents such as HIV,
hepatitis C, and Hansen’s disease. [1,3]
Leprosy is a chronic infection that is caused by Mycobacterium
leprae. The organism was identified in 1873 by Hansen. It is a
neuropathy itself that affects the nerve trunks and cutaneous
nerve endings leading to sensory, motor, and autonomic
neuropathies. Small fiber neuropathies occur initially whereas
the large fiber neuropathies occur late. The most common
associations of Hansen’s disease are with classical leprosy
neuropathy, pure neuritic leprosy, reactional leprosy neuritis,
painful small fiber neuropathy, leprosy late onset neuropathy,
autonomic neuropathy, and arthritic leprosy. [4‐6]
As of now, it has been hypothesized that lepra reaction may
lead to the exposure of neural antigens. These antigens may
lead to autoimmune reaction, thereby causing GB syndrome. [7,8]
Rarely, cases have been known that present as GB syndrome
without any evidence of lepra reaction. [9] To conclude, we
present a rare case of GB syndrome that was caused by
Hansen’s disease with no evidence of lepra reaction. To the
best of our knowledge, there have been only 1 report of similar
presentation reported in the past decade.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Saumya H Mittal, K C Rakshith, Z K Misri,
Shivanand Pai, Nisha Shenoy
Department of Neurology, KMC Hospital, Mangalore,
Karnataka, India
Address for correspondence:
Dr. Saumya H Mittal,
Department of Neurology, KMC Hospital, Mangalore,
Karnataka, India.
E‐mail: saumyamittal1@gmail.com
References
1. Walling AD, Dickson G. Guillain‐Barré syndrome. Am Fam
Physician 2013;87:191‐7.
2. van Doorn PA1, Ruts L, Jacobs BC. Clinical features, pathogenesis,
and treatment of Guillain‐Barré syndrome. Lancet Neurol
2008;7:939‐50.
3. Köller H, Kieseier BC, Jander S, Hartung HP. Chronic inflammatory
demyelinating polyneuropathy. N Engl J Med 2005;352:1343‐56.
4. Nascimento OJ. Leprosy neuropathy: Clinical presentations. Arq
Neuropsiquiatr 2013;71:661‐6.
Neurology India | January-February 2017 | Vol 65 | Issue 1 179

Letters to Editor
5. Cardoso Fde M, De Freitas MR, Escada TM, Nevares MT,
Nascimento OJ. Late onset neuropathy in leprosy patients released
from treatment: Not all due to reactions? Lepr Rev 2013;84:128‐35.
6. Cabalar M, Yayla V, Ulutas S, Senadim S, Oktar AC. The clinical and
neurophysiological study of leprosy. Pak J Med Sci 2014;30:501‐6.
7. Grover C, Kubba S, Nanda S, Kumar V, Reddy BS. Leprosy with
Guillain Barre syndrome: A new neurologic manifestation? J
Dermatol 2004;31:119‐33.
8. Rai VM, Shenoi S, Rao SN. Guillain Barré Syndrome like
presentation in borderline leprosy with type 2 reaction. Dermatol
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How to cite this article: Mittal SH, Rakshith KC, Misri ZK, Pai S,
Shenoy N. Guillain–Barré syndrome: A rare manifestation of Hansen's
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Novel SCN8A mutation in a girl with refractory
seizures and autistic features
Sir,
A 4‐year‐old girl presented with speech delay and refractory
seizures. She had no adverse perinatal events, had normal
motor milestones, and could speak only a few bisyllables.
She had seizures since 4 months of age. Initially, she had
generalized tonic–clonic seizures (2–3 episodes/week) and
required multiple anticonvulsant drugs (phenytoin, valproate,
lamotrigine, clobazam, and levetiracetam). After 14 months of
age, she experienced nocturnal tonic seizures (2–3 times/week)
and atypical absences (2–3/day), which continued until her
admission to our hospital. The seizures were only occasionally
associated with fever. In addition to having seizures, she
had autistic features (Childhood Autism Rating Scale score
of 32). Her physical examination was unremarkable. Magnetic
resonance imaging (MRI) of the brain was normal. Interictal
electroencephalogram (EEG) showed a slow background
activity with right frontopolar spike‐wave discharges.
Karyotype, array comparative genomic hybridization, plasma
acylcarnitine profile, and urine organic acids were normal. Next
generation sequencing for epilepsy genes [Table 1] revealed a
novel pathogenic heterozygous missense mutation (c.4214C>A;
p.Ala1405Asp) in the exon 22 of the SCN8A gene. Both the
parents were negative for this variant. She was again started
on phenytoin with resolution of tonic seizures, persistence of
atypical absences, and appearance of daily head‐drops. She was
started on modified Atkins diet. However, it had to be stopped
after 25 days in view of poor compliance and oral acceptance
by the child. Behavioural therapy was initiated and genetic
counselling was done.
Mutations in SCN8A, encoding one of the main voltage‐gated
sodium channel subunits (Nav1.6) in the brain, have been
recently described in patients with severe epilepsy and the
phenotype is still evolving. [1,2] Seventeen patients with de novo
heterozygous mutations of SCN8A were recently reported.
[2]
The phenotype comprised variable intellectual disability,
drug‐refractory epilepsy, autistic features, and prominent
motor manifestations (hypotonia, dystonia, hyperreflexia, and
ataxia). The mean age at the onset of seizures was 5 months
and the reported seizure types included focal, tonic, clonic,
myoclonic, atypical absence seizures, epileptic spasms, and
febrile seizures. Thus, the genetic testing for SCN8A should
be considered in children with unclassified severe epilepsy.
This may have a therapeutic implication. Four patients with a
missense SCN8A mutation and epilepsy were reported to have
a remarkably good response on high doses of phenytoin, and
loss of seizure control when the phenytoin medication was
reduced. [3] Our patient showed resolution of tonic seizures with
phenytoin; however, the other seizure types were unaffected.
Due to the recent advances in targeted next‐generation
sequencing panels for epileptic encephalopathy/epilepsy,
the diagnostic yield for an underlying genetic abnormality
has increased in patients with epileptic encephalopathy. The
diagnostic yields have been reported to be between 10 and 48.5%
in the literature for the 35 to 265 gene panels. [4] This technique
has helped us to achieve a diagnosis in the present case.
Table 1: Next Generation Sequencing for epilepsy gene panel
ADSL, PMM2, ARX, PNKP, SCN2A, PLCB1, SCN8A, KCNT1,
GABRA1, GRIN2B, CDKL5, SLC25A22, STXBP1, SPTAN1, SCN1A,
KCNQ2, PCDH19, ARHGEF9, GABRG2, GABRB3, CACNA1H,
GRIN2A, SCN1B, GABRD, SCN9A, CACNB4, CLCN2, SLC2A1,
EFHC1, ALDH7A1, CHD2, SCN2A, KCNQ3, MECP2, MEF2C,
FOXG1, CHRNA4, CHRNB2, CHRNA2, DEPDC5, CNTNAP2, LGI1,
CPA6, KCNMA1, SRPX2, KCNJ10, PNPO, SLC9A6 (48)
180 Neurology India | January-February 2017 | Vol 65 | Issue 1