Degeneración lobular frontotemporal: estudio descriptivo de 42 pacientes / Frontotemporal lobar degeneration: a descriptive study of 42 patients

Introducción. La degeneración lobular frontotemporal(DLFT) se considera la segunda causa de demencia presenil.A pesar del gran interés que ha generado en los últimosaños existen pocos estudios publicados en España.Métodos. Estudio descriptivo retrospectivo de 42 pacientescon DLFT evaluados en nuestra unidad durante elperíodo 1996-2006.Resultados. Treinta y un pacientes presentaban la variantefrontal de DLFT (DFT), ocho afasia progresiva no fluentey tres demencia semántica. La edad media de inicio fue 56años, el retraso diagnóstico 3,5 años y la supervivencia media6,8 años. El 35 % tenían historia familiar indicativa de demencia.En los pacientes con DFT la expresión clínica fue unacombinación de trastorno de conducta y personalidad juntocon alteración del lenguaje. La resonancia magnética mostróatrofia frontal y/o temporal en el 62% de los casos y la SPECThipoperfusión frontal y/o temporal en el 75%. En cuatro pacientes(dos de ellos hermanos) se detectó la mutación P301Lde tau y en otro la mutación A303AfsX57 de progranulina(PGRN). Se realizó necropsia a cinco pacientes, encontrándoseDLFT con inclusiones ubiquitina-inmunorreactivas (DLFT-U) yenfermedad de motoneurona en dos casos, DLFT-U con inclusionesintranucleares lanceoladas en el caso con mutación dePGRN y taupatía generalizada con predominio de isoformas4R en los otros dos, ambos con la mutación P301L.Conclusiones. Nuestros resultados son similares a losde las grandes series europeas. Debe sospecharse DLFT enpacientes preseniles con trastorno predominante y precozde la conducta y/o del lenguaje. La neuroimagen apoya eldiagnóstico en la mayoría de los casos. El gran impacto sociofamiliarde la DLFT, el inicio presenil, la alta frecuencia de antecedentesfamiliares de demencia y la posibilidad de realizarestudio y consejo genético realzan su importancia clínica (AU)

Introduction. Frontotemporal lobar degeneration (FTLD)is considered to be the second cause of presenile dementia.In spite of the great interest it has generated over the lastfew years, few studies have been published in our country.Methods. A descriptive retrospective study of 42 patientswith FTLD evaluated in our unit during the period1996-2006 was performed.Results. Thirty one patients presented with frontalvariant FTLD (FTD), eigth with non-fluent progressiveaphasia and three with semantic dementia. Mean age atonset was 56 years, diagnostic delay 3.5 years and meansurvival 6.8 years. 35% had a family history suggestiveof dementia. In patients with FTD the clinical expressionwas a combination of behavioral and personality disorderstogether with language impairment. Magnetic resonanceimaging showed frontal and/or temporal atrophy in62% of cases and SPECT showed frontal and/or temporalhypoperfusion in 75%. The P301L tau mutation was detectedin four patients (two of them siblings) and theA303AfsX57 progranulin mutation in one. Necropsy wasperformed in five patients, revealing FTLD with ubiquitininmunoreactiveinclusions (FTLD-U) and motor neuron diseasein two cases, FTLD-U with «cat’s-eye» shaped intranuclearinclusions in the case with the progranulinmutation and FTLD tauopathy with predominance of 4Rtau in the remaining two, both with the P301L mutation.Conclusions. Our results are similar to those of thegreat European series. FTLD must be suspected in presenilepatients with prominent behavioral and/or languagedisorders. Neuroimaging supports the diagnosis in themajority of cases. The huge sociofamiliar impact ofFTLD, presenile onset, high frequency of familial historyof dementia and possibility of genetic study and counse-69 ling highlight its clinical relevance (AU)

[Frontotemporal lobar degeneration: a descriptive study of 42 patients]. / Degeneración lobular frontotemporal: estudio descriptivo de 42 pacientes.

INTRODUCTION: Frontotemporal lobar degeneration (FTLD) is considered to be the second cause of presenile dementia. In spite of the great interest it has generated over the last few years, few studies have been published in our country. METHODS: A descriptive retrospective study of 42 patients with FTLD evaluated in our unit during the period 1996-2006 was performed. RESULTS: Thirty one patients presented with frontal variant FTLD (FTD), eigth with non-fluent progressive aphasia and three with semantic dementia. Mean age at onset was 56 years, diagnostic delay 3.5 years and mean survival 6.8 years. 35% had a family history suggestive of dementia. In patients with FTD the clinical expression was a combination of behavioral and personality disorders together with language impairment. Magnetic resonance imaging showed frontal and/or temporal atrophy in 62% of cases and SPECT showed frontal and/or temporal hypoperfusion in 75%. The P301L tau mutation was detected in four patients (two of them siblings) and the A303AfsX57 progranulin mutation in one. Necropsy was performed in five patients, revealing FTLD with ubiquitininmunoreactive inclusions (FTLD-U) and motor neuron disease in two cases, FTLD-U with <> shaped intranuclear inclusions in the case with the progranulin mutation and FTLD tauopathy with predominance of 4R tau in the remaining two, both with the P301L mutation. CONCLUSIONS: Our results are similar to those of the great European series. FTLD must be suspected in presenile patients with prominent behavioral and/or language disorders. Neuroimaging supports the diagnosis in the majority of cases. The huge sociofamiliar impact of FTLD, presenile onset, high frequency of familial history of dementia and possibility of genetic study and counseling highlight its clinical relevance.

Musk-antibody positive myasthenia gravis presenting with isolated neck extensor weakness.

Dropped head sign is characterized by the gradual forward sagging of the head due to weakness of neck extensor muscles. This may be a prominent sign of several neuromuscular disorders and may be an isolated feature of myasthenia gravis (MG). We describe a patient with isolated neck extensor weakness, eletrophysiological findings suggesting myasthenia gravis and positive MuSK antibodies. This case supports that finding anti-MuSK antibodies may be extremely helpful in dropped head patients and negative acetylcholine receptor antibodies especially if needle EMG does not reveal myopathic or neurogenic patterns.

[Cerebrotendinous xanthomatosis without tendinous xanthomas: presentation of two cases]. / Xantomatosis cerebrotendinosa sin xantomas tendinosos: presentación de dos casos.

Cerebrotendinous xanthomatosis (CTX) is a genetic disorder caused by a 27-hydroxilase enzyme deficiency, leading to beta-cholestanol storage in many body tissues. Clinically, the disease is characterised by the presence of tendinous xanthomas, juvenile cataracts and progressive neurologic dysfunction. The diagnosis requires beta-cholestanol quantification in serum. We report two siblings with a history of photosensitive epilepsy of childhood onset, who developed progressive spastic paraparesis and cataracts in their third decade of life. They were diagnosed to have CTX in spite of the absence of tendinous xanthomas. Cranial and spinal MRI only showed bilateral high intensity signal in the dentate nuclei in the T2-weighted and proton-density sequences. Our patients presented with a progressive spastic paraparesis. The delay in the diagnosis in our case could be due to the absence of tendinous xanthomas and late-onset cataracts. The recognition of the disease is important, because the treatment with chenodeoxycholic acid induces a decrement of beta-cholestanol levels in serum and could prevent the progression of the disease.

[Neuropathy by n-hexanes: a generalized disorder of the intermediate filaments]. / Neuropatía por n-hexanos: un trastorno generalizado de los filamentos intermedios.

BACKGROUND: Chronic inhalation of glues containing n-hexanes produces neurofilament (NF) accumulation which induces sensory-motor polyneuropathy. In vitro assays have shown this toxic substance causes intermediate filaments (IF) aggregation in non-neuronal cells. OBJECTIVE: To describe intermediate filament changes in human pathology due to n-hexanes. PATIENTS AND METHODS: Sural nerve and skin biopsy samples from 2 patients who suffered from a severe sensory-motor polyneuropathy after prolonged inhalation of glue containing n-hexane were examined with electron microscopy and vimentin and phosphorylated NF immunocytochemistry. RESULTS: Abnormal accumulations of NF and NF-immunoreactive products occurred in nerve fibers and increased numbers of fibrils were observed in endoneurial endothelial cells of the sural nerve. In addition, abnormal vimentin-immunoreactive deposition was seen in fibroblasts and capillaries of the skin. The present results suggest that high doses of n-hexane cause a diffuse IF disorder in a similar form as occurs in giant axonal neuropathy. CONCLUSION: IF aggregation can occur in non-neuronal cells in humans, as has been previously proved in in vitro experiments. The presence of IF accumulations in Schwann cells, as seen in the ultrastructural examination, together with the electrophysiological findings showing an early decrease of sensory and motor nerve conduction velocities, suggests the existence of a primary myelinic disorder associated with axonal damage.

[Centronuclear myopathy]. / Miopatía centronuclear.

A 19 year-old patient, second child of a non consanguinous marriage, was evaluated because of the patient progressive mental retardation and muscular weakness from infancy. Six maternal uncles non had died of unknown cause in the first year of life, and his mother had 3 spontaneous miscarriages; the two sisters of the patient were healthy. Clinical examination demonstrated a severe mental retardation, discrete proximal muscular weakness as well as universal areflexia. The muscular enzymes were elevated and the electrophysiologic study showed normal neurographic parameters and abundant generalized spontaneous activity with a mixed type contraction pattern. Histologic examination of the muscle was diagnosed as myopathy with atrophy of type I fibers and central nuclei and upon cranial nuclear magnetic resonance (NMR) images suggestive of perinatal hypoxic-ischemic encephalopathy were observed.