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Madras motor neuron disease is a form of motor neuron disease closely related to the Brown-Vialetto-Van Laere and Boltshauser syndromes. Characteristic features of this disease include facial and bulbar paralysis, sensorineural hearing impairment, asymmetrical weakness of limbs and pyramidal signs with a slow progression. Its variants have additional features including optic atrophy and cerebellar signs.

Symptoms

Madras pattern of motor neuron diseases (MMND) is often apparent at a young age and the symptoms include bulbar palsy, diffuse atrophy with weakness of limbs, and the symptoms are benign but apparent. There is also persistent asymmetrical limb involvement, which is seen in many individuals with MMND, along with sensorineural hearing impairment. MMND affects many cranial nerves, particularly involving the 7th (facial nerve) and 9th to the 12th cranial nerves (in order: glossopharyngeal nerve, vagus nerve, accessory nerve, spinal accessory nerve). Many individuals with MMND also experience muscular atrophy.

Etiology

Madras motor neuron disease (MMND) cases are mainly sporadic with a few families that exhibit familial Madras motor neuron disease (FMMND). In a study using 89 individuals that were diagnosed with sporadic MMND, 13 of them were found to have some of the same ancestors. In the same study that additionally looked at 16 families that displayed FMMND, three of the families were found to have some of the same ancestors. Through the simple usage of pedigree charts, it was hypothesized that the mode of inheritance of MMND is autosomal recessive in 15 of the 16 families studied, and autosomal dominant in the other. The exact etiology of MMND is unknown, however based off of familial studies along with the prevalence of sporadic cases primarily confined to southern India, there is support for both genetic and environmental causes. Through postmortem studies in persons with MMND, it has been consistently found that the spinal cord has extreme loss of anterior horn cells and demyelination and sclerosis of the ventrolateral columns; which could explain peripheral weakness, paresthesias, or paralysis. Changes are also found in the color of the myelin of the optic nerves, decreases in Purkinje cells, increase in Bergman glia, demyelination of fibers around the dentate nucleus with gliosis, swollen globular neurons of deep nuclei of the cerebellum, neural depletion and gliosis of the cochlear nucleus on both sides of the brainstem, and demyelination and axonal loss of the cochlear nerve. Because of the consistent findings of gliosis there is a strong argument that inflammation is one of the main causes of this disease, but again, the exact etiology is unknown.

Diagnostic methods

A neurologist would be the medical specialist someone with MMND would follow with. After an extensive history and physical examination, neuroimaging studies may help distinguish MMND from other motor neuron diseases. The differential diagnosis may include: ALS, spinocerebellar ataxia syndromes, Brown-Vialetto-Van Laere, progressive muscular atrophy, post-polio progressive muscular atrophy, and spinal muscular atrophy.

Management/Treatment

As of March 2017, there is no cure for MMND. However, symptomatic and supportive care are available to treat the symptoms of the disease.

Prognosis

The age of onset of Madras Motor Neuron Disease is variant ranging from 5 years old to over 20 - with an average age of onset at 16 years old. The prognosis of the individual is dependent on the symptoms present in that particular person at the time of onset. Their daily quality of life is initially expected to be retained when treated symptomatically with supportive care, but the disease does cause a progressive but benign decline. Mean survival duration (MSD) is also highly variable between patients, notably independent of age of onset. Between males and females, males have a higher MSD of 389.7 ± 32.4 months (about 32.5 years) and the MSD for women is 264.20 ± 30.92 months (about 22 years).

Epidemiology

The onset of MMND is often seen at a young age, with the average age of onset being 16 years old and occurs equally in males as it does in females. The incidence rate of MMND is less than 1 in 1,000,000. The vast majority of reported cases have been in Southern India, with the few others being reported in other parts of Asia and one in Europe.

History

Madras motor neuron disease was first described by Meenakshisundaram et al. in Madras, India in 1970.

Today, the area is known as Chennai. Subsequently, 29 separate cases were determined to be MMND. As of 2009, there were 157 known cases matching the physiological symptoms of the disease originally described by Meenakshisundaram and their team. 152 of these cases were present in South Indian states of Andhra Pradesh, Karnataka, Kerala, and Tamil Nadu, while the 5 others were individual cases in China, Italy, Korea, Thailand, and Turkey.

Map of India

The patient in Italy originated from South India whereas the other incidences seemed to originate independently.

Earliest incidences of the disease were thought to be sporadic, however, connections were shown to display a genetic inheritance. Since not every instance of MMND shows these familial inheritance patterns, this form has been characterized as Familial Madras Motor Neuron Disease (FMMND). There has also been determined to be a variant of the MMND, known as MMNDV.

Research

Due to the rareness of MMND, little research is currently being done to specifically combat the disease. However, research into motor neuron diseases like MMND may yield results pertinent to the treatment and understanding of MMND.

External Links

• Description and Survival Pattern of 116 patients from Southern India seen over 36 years (1971–2007)|
• is Distinct from the Riboflavin Transporter Genetic Defects that Cause Brown–Vialetto–Van Laere syndrome|