Clinical and pathological features of a Parkinsonian syndrome in a family with an Ala53Thr alpha-synuclein mutation.

We describe an Australian family of Greek origin with a parkinsonian syndrome and an Ala53Thr alpha-synuclein gene mutation. Five of 9 siblings were affected, the average age of onset was 45 years, and the initial symptoms were variable, including resting tremor, bradykinesia, and gait disturbance, as previously described in families with the same point mutation. Affected family members responded well to levodopa, developed progressive cognitive impairment, and had a disease duration of 5 to 16 years. Pathologic features typical of idiopathic Parkinson's disease were found at autopsy. However, there were several additional features not previously reported in families with this gene mutation. These features included severe central hypoventilation, orthostatic hypotension, prominent myoclonus, and urinary incontinence. An abundance of alpha-synuclein-immunoreactive Lewy neurites were found in the brainstem pigmented nuclei, hippocampus, and temporal neocortex. The Lewy neurites were associated with temporal lobe vacuolation. Subcortical basal ganglia cell loss and gliosis were seen. These additional clinical and pathological features suggest that the Ala53Thr alpha-synuclein mutation can produce a more widespread disorder than found in typical idiopathic Parkinson's disease.

Tension headache.

BACKGROUND: Tension headache and migraine are opposite ends of a benign recurrent headache spectrum. OBJECTIVE: To provide an approach to the diagnosis of benign recurrent headache. DISCUSSION: Tension headache is characterised by symmetry, non-disabling severity and the absence of vascular features (throbbing quality, nausea and photophobia). The differentiation between tension headache and attacks with more vascular features has important therapeutic implications as attacks with significant vascular features tend to respond better to antimigrainous approaches rather than those employed in the management of tension headache.

Voluntary muscle strength in hemiparesis: distribution of weakness at the elbow.

Maximal voluntary strength (torque) of the flexors and extensors of the elbow was measured in 56 normal subjects and 18 hemiparetic subjects. In normal subjects the ratio of extension to flexion strength averaged 55% and did not differ significantly between sides or sexes. The ratio of maximal extensor to flexor strength on the clinically unaffected side of hemiparetic subjects was the same as that for the normal subjects but it was significantly increased on the affected side. This increase indicates that the elbow flexors were relatively more weakened than the extensors on the hemiparetic side, a conclusion contrary to conventional clinical teaching. The increase in the ratio was not the result of co-contraction of either muscle group. A possible physiological basis for the observed distribution of weakness is suggested.

Headaches. A specialist's view.

Idiopathic, benign, recurrent or persistent headaches represent the overwhelming majority of headache problems presenting to the general practitioner. Many practitioners have an unrealistic fear of 'missing a tumour' which results in a tendency to pursue exhaustive investigation. With attention to the history detail, the clinician usually can categorise the headache accurately and reassure the patient and himself about its benign nature without the need for expensive and usually unhelpful tests.

A spinocerebellar degeneration with X-linked inheritance.

A spinocerebellar degeneration is described affecting ten members of a family over five generations with transmission by X-linked recessive inheritance. The clinical features include pes cavus, scoliosis, increased lumbar lordosis and signs of cerebellar dysfunction. There is a slowly progressive distal muscle atrophy, pyramidal weakness, brisk tendon jerks and the plantar responses are extensor. Sensory abnormalities were observed only in the two eldest members and consisted of mild impairment of position and vibration sense. A sural nerve biopsy showed loss of large diameter fibres and uniformly short internodal lengths as is usually found in Friedreich's ataxia. However, the electrophyisological findings of retained sensory action potentials and reduced motor conduction velocities contrast with those of Friedreich's ataxia. Post-mortem examination of one of the affected members revealed spinal cord pathology similar to that seen in Friedreich's ataxia with degeneration of the dorsal columns, and spinocerebellar and corticospinal tracts although the loss of Purkinje cells in the cerebellum was greater than is usually seen in that condition.

Effects of methysergide, pizotifen and ergotamine in the monkey cranial circulation.

Internal and external carotid vascular resistances were measured, in anaesthetized monkeys, to asses the direct cranial vascular effects of i.v. methysergide, pizotifen and ergotamine, and their effects on the cranial vascular responses to the constrictors 5-hydroxytryptamine and noradrenaline and the dilators histamine, prostaglandin E1 and bradykinin. Methysergide reduced responses to 5-HT, and tended to potentiate the external carotid responses to noradrenaline. Pizotifen blocked responses to histamine; it tended to reduce internal carotid responses to 5-HT, but it potentiated external carotid 5-HT responses. Ergotamine reduced responses to 5-HT and noradrenaline, but this was probably related to its cranial vasoconstrictor effects, especially in the external carotid circulation. Methysergide induced weak transient cranial vasoconstriction and pizotifen had no direct effects. These findings may be relevant to the therapeutic actions of these drugs in migraine, since the doses used approximated to those used clinically.

Internal and external carotid vascular responses to vasoactive agents in the monkey.

Internal and external carotid blood flows in anesthetized monkeys were measured simultaneously using electromagnetic flowmeters. Complete dose-response relationships were established for the effects of intracarotid infusion of several humoral agents implicated in migraine. Both the internal and external carotid vasculatures were constricted by serotonin and prostaglandin F2alpha and dilated by bradykinin, histamine, and acetylcholine. Noradrenalin and adrenaline constricted the external carotid vasculature but had little direct effect in the internal carotid territory. Prostaglandin E1 dilated the external carotid vasculature. Low doses of prostaglandin E1 produced dilation in the internal carotid circulation, but with higher doses there was a paradoxical abolition of this effect.