Frontal lobe dementia and motor neuron disease.

Neary, David; Snowden, Julie S.; Mann, Dave; Northen, B; Goulding, Peter; Macdermott, N.

doi:10.1136/jnnp.53.1.23

Cited by 408 publications

(188 citation statements)

References 29 publications

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“…1,2,27 FTLDs with tauopathy included Pick disease, 27 corticobasal degeneration, 27,28 progressive supranuclear palsy, 27 FTLD with MAPT mutations, also called frontotemporal dementia with parkinsonism linked to chromosome 17, 27 tangle-only dementia, 27 and argyrophilic grain disease. 31 Other cases fulfilling clinical and/or neuropathological diagnostic criteria for FTLD included neuronal intermediate filament inclusion disease, 32 hereditary diffuse leukoencephalopathy with spheroids, 33 and basophilic inclusion body disease.…”

Section: Tissue Collection and Processingmentioning

confidence: 99%

TDP-43 in Familial and Sporadic Frontotemporal Lobar Degeneration with Ubiquitin Inclusions

Cairns

Neumann

Bigio

et al. 2007

The American Journal of Pathology

470

482

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The frontotemporal dementias (FTDs) are a clinically, genetically, and neuropathologically heterogeneous group of diseases accounting for up to 20% of presenile dementia cases. FTD is characterized by behavioral and/or language dysfunction and may co-occur with motor neuron disease (MND).1,2 Frontotemporal lobar degeneration (FTLD) with ubiquitin-positive, tau-negative inclusions (FTLD-U) is the most common underlying pathology in FTD with and without MND.

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Section: Tissue Collection and Processingmentioning

confidence: 99%

TDP-43 in Familial and Sporadic Frontotemporal Lobar Degeneration with Ubiquitin Inclusions

Cairns

Neumann

Bigio

et al. 2007

The American Journal of Pathology

470

482

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“…In 5 to 10% of motor neuron disease (MND) cases, a frontotemporal type dementia (FTD) is present. 1 Here we show that CHMP2B (charged multivesicular body protein 2B), a gene that was recently shown to be linked to FTD, 2 was altered in two unrelated patients with ALSspectrum disorders. One mutation is predicted to alter a conserved functional domain.…”

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confidence: 99%

ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B)

Parkinson

Ince²,

Smith³

et al. 2006

Neurology

351

219

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Abstract-Mutation in the CHMP2B gene has been implicated in frontotemporal dementia. The authors screened CHMP2B in patients with ALS and several cohorts of control samples. They identified mutations (Q206H; I29V) in two patients with non-SOD1 ALS. Neuropathology of the Q206H case showed lower motor neuron predominant disease with ubiquitylated inclusions in motor neurons. Antibodies to p62 (sequestosome 1) showed novel oligodendroglial inclusions in the motor cortex. NEUROLOGY 2006;67:1074-1077 1 Here we show that CHMP2B (charged multivesicular body protein 2B), a gene that was recently shown to be linked to FTD, 2 was altered in two unrelated patients with ALSspectrum disorders. One mutation is predicted to alter a conserved functional domain. Pathology from this case strengthens the hypothesis of a common molecular pathology between ALS and FTD. 3 The second case showed a point substitution that has been previously described as a low-frequency variation in the CHMP2B gene. A 75-year-old man reported bulbaronset weakness for 11 months, which progressed to involve his hands after 5 months. Examination findings at that stage were a wasted, weak, fasciculating tongue, flaccid dysarthria, and bilateral weakness and wasting of the intrinsic hand muscles. Tendon reflexes were depressed, and the plantar responses were flexor. There was no evidence of significant cognitive dysfunction on bedside testing. He had a right below-knee amputation for trauma 15 years previously. Neurophysiology showed widespread neurogenic changes in bulbar, upper limb, and lower limb territories, and a diagnosis of progressive muscular atrophy (PMA) (El Escorial category of suspected ALS) was made. His weakness rapidly progressed until his death from respiratory failure 15 months after symptom onset. There was no evidence of extramotor neurologic signs or symptoms or dementia throughout the illness. A cousin was also said to have died of ALS, but it was not possible to obtain DNA from other family members.Patient 2. This 65-year-old man had behavioral and personality changes, including depression, excessive alcohol consumption, and inappropriate sexual behavior. In the next 4 years, this progressed to fulminant FTD. After 5 years, he developed motor disturbances including atrophy of the tongue and facial muscles. There was spastic dysarthria, pseudobulbar paresis causing dysphagia, and weight loss. Motor symptoms progressed to paresis of the right arm and hand and both legs. He retained normal sensation and autonomic function. There were brisk tendon reflexes and upgoing plantar responses. A diagnosis of ALS (El Escorial ALS ϩ dementia) was established on clinical and neurophysiologic grounds. Six years after the onset of behavioral symptoms, he died suddenly, but no autopsy was performed. His father was reported to have frontal lobe dysfunction and motor disturbances. This familial history was not verified by case note review, and DNA could not be obtained from other family members because of lack of permission.

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“…Language impairment has been reported in ALS and ALS-FTD, 21 although without appropriate tools the presence of dysarthria may confound analysis of higher language in these disease groups. Pathological involvement of the left temporal lobe (including the temporal pole and the peri-insular region) and frontotemporal white matter connections, 22 have been reported in ALS and ALS-FTD.…”

Section: Introductionmentioning

confidence: 99%