Large deletion mutation of SPAST in a multi-generation family from Sardinia.

BACKGROUND AND PURPOSE: The hereditary spastic paraplegias (HSP) are characterized by progressive spasticity of the lower limbs, mostly inherited as an autosomal dominant trait. Analyses of large HSP pedigrees could help to better characterize the phenotype due to a single causative mutation. Patients in a seven-generation kindred carrying a large deletion in SPAST/SPG4 are described. METHODS: Individuals originating from Sardinia were clinically and genetically studied. RESULTS: Sixty-seven subjects carried a heterozygous deletion encompassing exons 2-17 of SPAST. Fifty patients (53.2 ± 15.4 years) presented a pure form of spastic paraparesis characterized by mild impairment and slow progression. Most patients showed spasticity, increased tendon reflexes in the lower limbs and Babinski sign, whilst weakness was rarely detected and urinary disturbances occasionally reported. Amongst the 17 asymptomatic carriers of the mutation, minimal neurological signs were detected in 11 cases. CONCLUSIONS: A focus on spasticity, increased tendon reflexes and Babinski sign, more than on weakness, could help clinicians to promote early diagnosis in asymptomatic carriers of SPAST deletions.

Paired neurophysiological and clinical study of the brainstem at different stages of Parkinson's Disease.

OBJECTIVE: To study brainstem function in Parkinson's Disease (PD) at different stages, through a battery of vestibular-evoked myogenic potentials (VEMPs) and compare the results with scores on clinical scales assessing the presence of symptoms linked to brainstem involvement. METHODS: Cervical, masseter and ocular VEMPs were recorded in patients with early PD (n=14, disease duration 1.42±0.7years), advanced PD (n=19, disease duration 7.26±2.9years) and in 27 age-matched controls. In PD, the following clinical scales were administered: Mini-BESTest, REM sleep Behavior Disorder Screening Questionnaire (RBD-SQ), PD Sleep Scale, Epworth Sleepiness Scale and Geriatric Depression Scale. RESULTS: Rate of VEMPs alterations was higher (p<0.001) in PD than controls, but similar within PD groups. However, early and advanced PD showed a different pattern of abnormalities (p=0.02), being latency delay prevalent in the former and absence in the latter. VEMP impairment correlated directly with RBD-SQ scores in both PD cohorts and inversely with Mini-BESTest scores in advanced PD. CONCLUSIONS: VEMPs displayed progressive severity of alterations at different stages of PD, with remarkable correlations with presence of postural instability and RBD. SIGNIFICANCE: The combined use of VEMPs may provide interesting insights into the pathophysiological mechanisms of PD at the earliest and prodromal stage of the disease.

Successful treatment of acquired pendular elliptical nystagmus in multiple sclerosis with isoniazid and base-out prisms.

We treated 3 multiple sclerosis patients who had pendular nystagmus with isoniazid (800 to 1,000 mg/d). Isoniazid abolished the nystagmus and relieved oscillopsia in 2 patients but was ineffective in the 3rd in whom the nystagmus was damped with convergence and vision improved with converging (base-out) prisms.

Incidence of multiple sclerosis in the town of Sassari, Sardinia, 1965 to 1985: evidence for increasing occurrence of the disease.

Prevalence studies carried out in Sardinia from 1975 suggest an increasing occurrence of MS. However, it is questionable whether this increase represents a real change in MS incidence or simply reflects longer survival. Data from 79 patients indicated the average annual incidence for the period 1965 through 1985 was 3.4 per 100,000. On December 31, 1985, the prevalence rate was 69 per 100,000. Evaluation of MS temporal trends showed a significant increase in MS incidence during the study period: values ranged around two per 100,000 in the triennial periods 1965-1967, 1968-1970, and 1971-1973, and around five in each triennium from 1977 onward.

Treatment of cerebellar tremors with carbamazepine: a controlled trial with long-term follow-up.

We studied the effects of carbamazepine (CBZ) (400 and 600 mg per day) in 10 patients with cerebellar tremors in a single-blind manner. All patients improved on a clinical rating scale and by accelerometric recording; there was no improvement with placebo. Our data suggest that CBZ may be a valuable drug in cerebellar tremors.

Amnesia in a patient with bilateral lesions to the thalamus.

A case of anterograde amnesia is described in a 38-yr-old man with bilateral thalamic lesions. The patient appeared to have suffered no general intellectual loss and performed normally on standard memory tasks involving immediate recall of new material. There was, however, consistent impairment in recalling material, verbal and non-verbal, over delays as brief as a few seconds. Impairment was especially marked on tests involving free recall and partial cueing procedures; recognition memory was also impaired. Premorbid memory tested normally and susceptibility to interference was less than in other organic amnesics. Various interpretations of the patient's amnesia were considered but a deficit at the initial stages of information processing appeared to be indicated.

Epileptic laughter: electroclinical and cinefilm report of a case.

A woman, aged 30, experienced attacks of pathological laughter which began during the first months of life; they meet the qualifying criteria of epileptic laughter. Several attacks were recorded by polygraphy and cinefilm. The attack begins with a feeling of unreality associated with a forced, involuntary smile progressing to full laughter. The patient tried to mask the laughter which was not accompanied by euphoria but was followed by loss of consciousness and automatisms. Only during the latter phase of the previously normal EEG did an ictal discharge appear over the right hemisphere. On the basis of the electroclinical pattern and of a review of the literature, the seizure is tentatively explained in terms of a progressive ictal involvement of temporodiencephalic structures.

Alexia without agraphia: a study of a case of verbal alexia without accompanying colour-naming defect.

A 47-year-old man developed a persistent form of alexia without agraphia as the result of a haemorrhagic intracerebral lesion in the left inferior temporo-occipital region, due to the rupture of an arteriovenous malformation. Surgical evacuation of the haematoma and excision of the malformation did not produce any modification of the reading deficit, which remained unchanged during a 4-year follow-up. The reading deficit was restricted to words and the patient was able to read only letter-by-letter, so that the whole words were reconstructed from the auditory names of the letters. So far, the disconnection explanation is the standard explanation of alexia without agraphia and the present case of verbal alexia may be regarded as being within this overall category. However, this explanation meets with unanswered questions that suggest more flexible interpretations. Neurolinguistic studies have questioned the unique character of alexia without agraphia as a clinical entity and, in contrast to the disconnection hypothesis, support the notion that the different varieties of alexia that are traditionally described represent distinctive syndromes, each with its own clinical features and pathophysiological basis. In this context, the reading properties in this case seem fully compatible with a deficit of the visual word-form system postulated by Warrington and Shallice, that is, the relatively early stage of the reading process through which a word-form or equivalent unit is attained. This system might be lateralized to the left hemisphere, as suggested by the fact that this case, like other cases of verbal alexia, had sustained damage to the left hemisphere and did not show any differential preservation of the reading of concrete words.

Upbeat nystagmus as an early sign of cerebellar astrocytoma.

A boy with a left-hemispheric cerebellar astrocytoma had upbeat nystagmus exhibiting increasing-velocity slow phases. The nystagmus improved after excision of the tumour.

Efficacy of carbamazepine on cerebellar tremors in patients with superior cerebellar artery syndrome.

Three patients with postural and intention cerebellar tremor caused by a cerebellar infarction in the superior cerebellar artery distribution were studied; treatment with carbamazepine resulted in marked improvement.

Risperidone, neuroleptic malignant syndrome and probable dementia with Lewy bodies.

1. Conflicting reports are available regarding the sensitivity of patients with Dementia with Lewy bodies (DLB) to risperidone. 2. The authors studied a rare familial case of probable DLB, who developed a documented episode of neuroleptic malignant syndrome (NMS) following the exposure to risperidone. Previously, the patient had had an episode of NMS on trifluoperazine. 3. The discontinuance of risperidone, in combination with a mild increase of dopaminergic therapy, led to a complete recovery in few days. 4. In patients with DLB, a continued vigilance for extrapyramidal side effects, including NMS, would be advisable during the use of risperidone.

Early manifestations of dementing illness: treatment with glycosaminoglycan polysulfate.

1. In a multicenter, placebo-controlled, double-blind clinical trial in 156 elderly patients with psychopathologic symptoms, glycosaminoglycan polysulfate was found to be a therapeutically effective agent in the treatment of the earliest manifestations of a dementing process. 2. Treatment with glycosaminoglycan polysulfate in the daily dosage of 600 LRU, administered on the basis of a divided dosage schedule for 24 weeks, was significantly superior to an inactive placebo on several outcome measures including the SCAG Total and factor scores (i.e., Cognitive Dysfunction, Withdrawal, Agitation/Irritability and Depression), the NOWLIS Total and Fatiguability factor scores, the MMSE, the HAM-D Total and Vegetative Symptoms factor score and the CGI Severity of Illness and Global Improvement. 3. The drug was well tolerated; vital signs and laboratory measures did not show clinically significant changes within the experimental period.

Spontaneous involution of optic pathway lesions in neurofibromatosis type 1: serial contrast MR evaluation.

PURPOSE: To evaluate with contrast MR the evolution in size, signal, and contrast enhancement of optic pathway lesions in four patients with neurofibromatosis type 1. METHODS: The four reported patients are children with ages ranging from 21 months to 13 years affected by neurofibromatosis type 1 and optic pathway lesions. No treatment of the optic pathway lesions was carried out in these patients. They have been followed by serial contrast MR. RESULTS: In all patients a change in size, signal, and enhancement of optic pathways lesions was noted with time, and in the last follow-up study a marked reduction in size and enhancement of optic pathway lesions was observed in all cases. CONCLUSIONS: Modification and regression of optic pathway lesions with spontaneous disappearance of the enhancement is demonstrated. This finding could have a crucial influence on the therapeutic approach of the optic pathway lesions.

Ictal prosopagnosia and epileptogenic damage of the dominant hemisphere. A case history.

This case report concerns a patient whose episodes of prosopagnosia appeared to be epileptic manifestations arising from the left occipital lobe. The underlying pathology, as revealed by radiologic and surgical findings, was an atrophic-hypoplastic lesion of the left hemisphere, more prominent in the posterior sections, likely dating from early life. Removal of an arachnoidal cyst of the occipital pole and excision of the damaged gray matter were followed by the disappearance of the prosopagnosic seizures for the two years between the date of the surgical intervention and the publication of this article.

Neuro-ophthalmology.

Eye movement research during the last year is discussed. The review covers the fields of: memory-guided saccades in supplementary motor area lesions, and the vertical saccadic system; cerebral hemispheric localization of smooth pursuit asymmetry; oculomotor disturbances in Wallenberg's syndrome; locomotory gaze instability in vestibular dysfunction; smooth pursuit disorders in vermal infarct; physiologic end-point and rebound nystagmus and the results of surgical and optical treatment of manifest latent nystagmus; clinical/magnetic resonance imaging correlations in abnormalities of horizontal gaze; mesencephalic cholinergic nuclei in progressive supranuclear palsy; as well as mesencephalic damage in diabetic third nerve palsy, divisional oculomotor nerve paresis; and new hypotheses on eye muscle susceptibility in myasthenia gravis.