Madras Motor Neuron Disease
Motor
neurons are a type of cells in the nervous system that conveys impulses which directly
or indirectly control muscle movements.
Madras Motor Neuron Disease (MMND), also referred to as Madras
pattern motor neuron disease, is a rare young age
onset progressive neuromuscular
disease taking relatively benign course.
MMND has predominant geographic distribution in southern India.
Originally
identified in 1970 in the southern city of Madras, India, there are 152 MMND
cases have been reported from India until 2009. Outside this core region, as of 2009, solitary
cases of each in China, Italy, Korea, Thailand and Turkey have also been
reported, totaling 157 cases throughout the world. MMND is equally
represented in both sexes. Nearly all of them are
from four southern Indian states of Andhra Pradesh, Karnataka, Kerala and Tamil
Nadu
Molecular pathogenesis of the
condition is the unanswered important question in MMND and no published
scientific report is available in this respect. Multipronged approach is
required to evaluate various causal factors such as the genetic, environmental
and perhaps ethnic factor as well, considering its geographic preponderance.
Majority of the patients look
slender. The hallmark of MMND is sensorineural deafness (hearing loss due to
nerve defect), atrophy and weakness of the limb muscles, cranial nerve palsies
involving cranial nerves VII, IX and XII, facial and bulbar muscles (kind of
muscles that control the
chewing, swallowing and speech) with disease onset at young age (generally
before the age of 15). In addition to above symptoms a variant of MMND (MMNDV)
is presented with bilateral optic atrophy (loss of optic nerve fibers on both
sides) or visual impairment. Though majority of the MMND cases appear to be
sporadic, a few familial cases (FMMND) have been identified as well. While
recognizing the paucity in familial cases, the mode of inheritance within FMMND
is suggested to be predominantly autosomal recessive.
Table 1.
Select clinical characteristics from a large group of MMND patients. Excerpted
from a detailed scientific study in J Neurol Sci.
2008;269:65-73.
|
Clinical characteristics
|
n = 116
|
|
Average age at onset
|
16 years
|
|
Sensorineuronal deafness
|
91%
|
|
Bifacial weakness
|
51%
|
|
Bilateral visual impairment
|
13%
|
|
Bilateral optic atrophy
|
26%
|
|
Atrophy and weakness:
- distal
upper limb
- distal lower limb
|
100%
100%
|
|
Babinski's sign
|
62%
|
|
Male, female distribution ratio
|
1:1
|
Biochemical study: Low
plasma citrate and elevated pyruvate levels and resulting low citrate/pyruvate
ratio have been observed in a group of four MMND patients compared to normal
subjects. But this observation is yet to be reproduced and is currently not
considered to be of diagnostic significance.
Pathological study:
Observations on postmortem spinal cord reveal an extreme loss of anterior horn
cells, demyelination and sclerosis of the ventrolateral columns. Bulbar motor
nuclei and cochlear nucleus show neuronal depletion. Inflammatory etiology in
MMND is suggested.
MMND, a subgroup of broader
group called MND (motor neuron disease), closely resembles several other disease
conditions, including relatively common ALS (amyotrohic lateral sclerosis) and
are considered in the differential diagnosis. There are arguments if MMND and
Brown-Vialetto-Van Laere syndrome (BVVL) described from Western Europe are
similar clinical entities. However, there are several finer clinical features
that differentiate MMND from BVVL.
Figure 1.
A schematic of closely related diseases within MND. Grey shades relate clinical
proximity among the diseqases. This chart is based on differential diagnostic
algorithm described for BVVL syndrome in Orphanet J
Rare Dis. 2008;3:9.
There is no specific treatment for MMND is available yet. Intravenous
immunoglobulin administered in one case showed moderate improvement in certain
symptoms. Yet, immunoglobulin treatment is based on the assumption of
inflammatory etiology of MMND, but not a proven treatment. Rarity of MNND in
itself is an impediment for evolving a possible treatment. Symptomatic treatment
and supportive care, such as offering hearing aids, are part of MMND management
that might help maintain patients' routine activities. The positive aspect of
this disease is that many patients continue to live for several decades after
the onset of the disease.
References and further readings
Meenakshisundaram E,
Jagannathan K, Ramamurthi B.
Clinical pattern of motor neuron disease seen in younger age groups in Madras.
Neurol India. 1970;18(Suppl.1):109-112.
Valmikinathan K, Mascreen M,
Meenakshisundaram E, Snehalatha C.
Biochemical aspects of motor neurone disease--Madras pattern.
J Neurol Neurosurg Psychiatry. 1973;36:753-756.
Shankar SK, Gourie-Devi M,
Shankar L, Yasha TC, Santosh V, Das S.
Pathology of Madras type of motor neuron disease (MMND)--a histological and
immunohistochemical study. Acta Neuropathol.
2000;99:428-434.
Nalini A, Yamini BK, Gayatri
N, Thennarasu K, Gope R.
Familial Madras motor neuron disease (FMMND): study of 15 families from southern
India. J Neurol Sci. 2006;250:140-146.
Nalini A, Thennarasu K,
Yamini BK, Shivashankar D, Krishna N.
Madras motor neuron disease (MMND): clinical description and survival pattern of
116 patients from Southern India seen over 36 years (1971-2007).
J Neurol Sci. 2008;269:65-73.
Sathasivam S.
Brown-Vialetto-Van Laere syndrome. Orphanet J Rare
Dis. 2008;3:9.
