Hereditary spastic paraplegia with cerebellar ataxia: a complex phenotype associated with a new SPG4 gene mutation.

Complex forms of hereditary spastic paraplegia (HSP) are rare and usually transmitted in an autosomal recessive pattern. A family of four generations with autosomal dominant hereditary spastic paraplegia (AD-HSP) and a complex phenotype with variably expressed co-existing ataxia, dysarthria, unipolar depression, epilepsy, migraine, and cognitive impairment was investigated. Genetic linkage analysis and sequencing of the SPG4 gene was performed and electrophysiologic investigations were carried out in six individuals and positron emission tomography (PET) in one patient. The disease was linked to the SPG4 locus on chromosome 2p as previously reported for pure HSP. Sequence analysis of the SPG4 (spastin) gene identified a novel 1593 C > T (GLN490Stop) mutation leading to premature termination of exon 12 with ensuing truncation of the encoded protein. However, the mutation was only identified in those individuals who were clinically affected by a complex phenotype consisting of HSP and cerebellar ataxia. Other features noted in this kindred including epilepsy, cognitive impairment, depression, and migraine did not segregate with the HSP phenotype or mutation, and therefore the significance of these features to SPG4 is unclear. Electrophysiologic investigation showed increased central conduction time at somatosensory evoked potentials measured from the lower limbs as the only abnormal finding in two affected individuals with the SPG4 mutation. Moreover, PET of one patient showed significantly relatively decreased regional cerebral blood flow in most of the cerebellum. We conclude that this kindred demonstrates a considerable overlap between cerebellar ataxia and spastic paraplegia, emphasizing the marked clinical heterogeneity of HSP associated with spastin mutations.

[Thrombolytic treatment of acute cerebral infarction]. / Trombolysebehandling af akut cerebralt infarkt.

INTRODUCTION: Thrombolytic therapy of acute ischaemic stroke within three hours of the onset of symptoms is approved by health authorities in the USA and Canada, but not in Europe. METHODS: We report seven patients treated with recombinant tissue plasminogen activator (rtPA) within three hours of the onset of stroke according to an open protocol following internationally accepted guidelines. RESULTS: Three patients with initial severe neurological deficits made an almost complete recovery within the first 24 hours after treatment. Two patients had a partial remission, and two patients had no benefit. There were no bleeding complications. DISCUSSION: The present results are in accordance with the Cochrane Library's analysis of published data regarding thrombolytic therapy.

Machado-Joseph disease in three Scandinavian families.

Machado-Joseph disease (MJD) is an autosomal dominantly inherited neurodegenerative disorder characterized by varying age of onset and pronounced phenotypic heterogeneity. The clinical core features include gait ataxia, external ophthalmoplegia, nystagmus, and bulging eyes. Recently, Kawagushi et al. (1994) cloned the MJD1 gene on chromosome 14 and MJD turned out to be the fifth neurodegenerative disease caused by an unstable CAG repeat expansion. We have studied two large Danish families and one Norwegian family with MJD. Three features not previously associated with MJD are reported: dementia, generalized muscle and joint pain, and in one case neuropathological examination revealed atrophy of the inferior olives. We found a significant inverse correlation between age of onset and the length of the CAG repeat expansion, and anticipation is described through four succeeding generations. Instability of the CAG repeat expansion was most pronounced at paternal transmission.

The MS Impairment Scale: a pragmatic approach to the assessment of impairment in patients with multiple sclerosis.

We developed a measurement scale for assessment of impairment in MS patients (MSIS) in accordance with the recommendations of WHO. The items were kept close to a standard neurologic examination, and a short battery of cognitive tests was added. Normality was assigned to the value, zero, and the theoretical maximum score was 204. Two-hundred and ten multiple sclerosis (MS) patients were rated by one neurologist on the MS impairment Scale (MSIS), the Extended Disability Status Scale (EDSS), and the Ambulation Index (AI). The median MSIS score was 52 (5-147), the median EDSS 6.5 (1-9.5), and the median AI 5 (1-5). The relation between the MSIS scores and the EDSS was best described by an exponential function (non-linear regression coefficient, R = 0.87). Sixty-two of the patients were reexamined and rated by another neurologist. The interrater reliability coefficient (R) of the MSIS was 0.95, of the EDSS 0.91, and of the AI 0.94. Forty patients were examined twice by the first neurologist. The intrarater reliability coefficient was 0.97 for the MSIS, 0.95 for the EDSS, and 0.98 for the AI. The MSIS is easy to use and is robust to observer dissimilarities. It has a monomodal univariate distribution and has a better discriminatory power than the EDSS, especially in the EDSS range 6-9, while the interrater reliability of the MSIS is at least as good as that of the EDSS and the AI.

[Gilles de la Tourette syndrome]. / Gilles de la Tourette syndrom.

Gilles de la Tourette syndrome has its onset in childhood and is characterized by chronic motor and vocal tics and also complex tics. It is a lifelong illness with shorter and longer fluctuations in its severity. During puberty an aggravation in number and severity of tics is often observed, while symptoms in the third decade are reported to fade to some extent. The syndrome is found among all social classes, the male to female ratio is three to one, and it is probably inherited as an autosomal single dominant gene with varying penetrance. Gilles de la Tourette syndrome was earlier thought to be rare, but during the last years less pronounced cases have been seen. The etiology is not known, but a relative dopaminergic overactivity is a likely mechanism. It is possible to treat the symptoms with neuroleptics.

Megalocornea and mental retardation syndrome: a new case.

We report on a new case of the megalocornea mental retardation syndrome, first described by Neuhäuser et al. [1975]. Our patient had mental and motor retardation, megalocorneae, short stature, congenital hypotonia, frontal bossing, micrognathia, a cafe-au-lait spot, and ear anomalies. A literature survey is provided.