Kii ALS / PDC - Muro disease -

【Disease concept】

1. Regional distribution of the disease

Current and previous inhabitants of Muro district and surrounding areas of the Kii peninsula in Wakayama and Mie prefectures; i.e., south of the geographical line between Tanabe City in Wakayama prefecture and Matsuzaka City in Mie prefecture.

2. Clinical forms and symptoms

There are two clinical forms: ALS type and PDC type. ALS type presents with upper and lower motor neuron signs, including muscle atrophy, fasciculation, increased tendon reflexes, and the Babinski sign. These features are similar to those of classic ALS.

PDC type presents with parkinsonism (the major symptoms are akinesia and muscle rigidity, with occasional tremor, and unresponsiveness to L-dopa) and/or dementia (frontal subcortical cognitive symptoms such as abulia). PDC type may be accompanied by ALS symptoms.

3. Neuropathological findings

ALS type shows the typical neuropathological findings of ALS. PDC type presents with substantia nigra degeneration and basal ganglionic degeneration. PDS type is associated with a great abundance, while ALS type is associated with fewer, neurofibrillary tangles. Neurofibrillary tangles were shown to be abundant in the nucleus of the brainstem tegmentum, substantia nigra, nucleus of Meynert, diencephalon, and medial temporal lobe. The distribution is wide, exceeding that associated with the aging process. Some patients with PDC present with typical neuropathological findings of ALS. Although some patients have amyloid senile plaques, accumulation of tau protein is one of the major characteristics.

【Diagnostic criteria of Kii ALS/PDC】

1. Current and previous inhabitants of Muro district and surrounding areas of the Kii peninsula in Wakayama and Mie prefectures; i.e., south of the geographical line between Tanabe City in Wakayama prefecture and Matsuzaka City in Mie prefecture.

2. Clinical forms

　a.     ALS type: classic ALS type

　b.     PDC type: progressive parkinsonism (unresponsive to L-dopa) and/or dementia (abulia is observed even in the early stage)

　c.     ALS/PDC type: combination of a and b

3. Family history of ALS/PDC (ALS only, PDC only, or ALS and PDC)

4. Neuropathological findings

　a.     Classic ALS neuropathology, and neurofibrillary tangles in cerebral cortex and brainstem which exceed those that would be present due to the aging process

　b.     Substantia nigra degeneration, basal ganglionic degeneration, plus abundant neurofibrillary tangles in the cerebral cortex and brainstem which exceed those that would be present due to the aging process

　c.     a+b.

Possible: Any of (1+2a) or (1+2b)

Probable: Any of (1+2c), (1+2a+3), or (1+2b+3)

Definite: (Possible or Probable) and any of (4a), (4b), or (4c)

【Severity grade】

Ⅰ     Independent in daily life and maintaining a social life.

Ⅱ     Almost independent in daily life but have a difficulty with social life, working, household chores, or other physical activities.

Ⅲ     Unable to walk outside without a brace or assistance and needing minor assistance in daily life

Ⅳ     Bedridden or wheelchair-bound, but able to communicate, and able to eat and eliminate with assistance.

Ⅴ     Essentially bedridden and needing full assistance in daily life.

The concept and clinical diagnostic criteria were authorized by Japanese Society of Neurology.