ALS in Finland

ALS = amyotrophic lateral sclerosis; C9pos = carrier of the hexanucleotide repeat expansion in the C9orf72 gene; FALS-A = familial ALS, only first- and second-degree relatives with ALS (A) were considered in the definition of FALS; FTD = frontotemporal dementia; SALS-A = sporadic ALS; SBMA = spinobulbar muscular atrophy; SMAJ = spinal muscular atrophy Jokela type; Unk = noncarrier. SALS-NP/FALS-NP = broad definition, first- and second-degree relatives with various neurologic and psychiatric (NP) disorders were included in FALS-NP. FALS-A was classified in 158 families, C9pos in 91 (58%), Unk in 41 (26%), and SOD1 p.D91A in 26 (16%) families. FALS-NP was classified in in 326 families, of which 167 (51%) families were C9pos, 126 (39%) Unk, and 33 (10%) SOD1 p.D91A. Respiratory-onset cases were considered outliers in survival and were excluded from the phenotype analysis. FALS-NP categorization included the following neurologic disorders: ALS, FTD, Alzheimer disease, Lewy body disease, other dementia or cognitive deficit not linked to vascular or traumatic etiology, Parkinson disease, and Huntington disease. Neurodegenerative conditions such as corticobasal degeneration and multiple system atrophy as well as disorders causing muscular weakness or stiffness such as polyneuropathies, myasthenia gravis, myasthenic syndromes, and Stiff-person syndrome were grouped. We did not include mild cognitive deficits, unspecified memory problems, tremors, ataxias, seizures, epilepsies, stroke, severe trauma, post-polio syndrome, multiple sclerosis, migraine, congenital disorders, metastases, primary tumors of the nervous system, anecdotal recollections of autism-type disorders, and very late-onset dementias, i.e., when the relative was known or suspected to develop dementia at age 80 years or over. FALS-NP categorization included the following psychiatric conditions: schizophrenia, psychosis, delusions, bipolar disorder, significant alcohol or narcotics abuse/dependence, and suicide. Mood disorders were grouped (anxiety and depression when severe and diagnosed before the index patient was diagnosed with ALS). We did not include anecdotal mental problems, character disorders, obsessive-compulsive disorder, unspecified apathy, and recital faux pas.