Validating the portal population of the United Kingdom Multiple Sclerosis Register.

The UK Multiple Sclerosis Register (UKMSR) is a large cohort study designed to capture 'real world' information about living with multiple sclerosis (MS) in the UK from diverse sources. The primary source of data is directly from people with Multiple Sclerosis (pwMS) captured by longitudinal questionnaires via an internet portal. This population's diagnosis of MS is self-reported and therefore unverified. The second data source is clinical data which is captured from MS Specialist Treatment centres across the UK. This includes a clinically confirmed diagnosis of MS (by Macdonald criteria) for consented patients. A proportion of the internet population have also been consented at their hospital making comparisons possible. This dataset is called the 'linked dataset'. The purpose of this paper is to examine the characteristics of the three datasets: the self-reported portal data, clinical data and linked data, in order to assess the validity of the self-reported portal data. The internet (n = 11,021) and clinical (n = 3,003) populations were studied for key shared characteristics. We found them to be closely matched for mean age at diagnosis (clinical = 37.39, portal = 39.28) and gender ratio (female %, portal = 73.1, clinical = 75.2). The Two Sample Kolmogorov-Smirnov test was for the continuous variables to examine is they were drawn from the same distribution. The null hypothesis was rejected only for age at diagnosis (D = 0.078, p < 0.01). The populations therefore, were drawn from different distributions, as there are more patients with relapsing disease in the clinical cohort. In all other analyses performed, the populations were shown to be drawn from the same distribution. Our analysis has shown that the UKMSR portal population is highly analogous to the entirely clinical (validated) population. This supports the validity of the self-reported diagnosis and therefore that the portal population can be utilised as a viable and valid cohort of people with Multiple Sclerosis for study.

Trigeminal cephalgias and facial pain syndromes associated with autonomic dysfunction.

Trigeminal autonomic cephalgias (TACs) include a spectrum of primary headache syndromes associated with cranial autonomic dysfunction. Other types of headache and facial pain syndromes can be associated with marked localized facial or ear autonomic changes. We report on a group of patients suffering from episodic migraine with cranial autonomic features, patients with different presentations of the 'red ear syndrome' (RES), cluster headache with prominent lower facial involvement and crossover cases. In our experience crossover between TACs and migraine, RES and cluster headache is not uncommon. We propose that all these conditions belong to the same group and a unifying causative mechanism is proposed.

Kufor-Rakeb syndrome, pallido-pyramidal degeneration with supranuclear upgaze paresis and dementia, maps to 1p36.

Kufor-Rakeb syndrome is an autosomal recessive nigro-striatal-pallidal-pyramidal neurodegeneration. The onset is in the teenage years with clinical features of Parkinson's disease plus spasticity, supranuclear upgaze paresis, and dementia. Brain scans show atrophy of the globus pallidus and pyramids and, later, widespread cerebral atrophy. We report linkage in Kufor-Rakeb syndrome to a 9 cM region of chromosome 1p36 delineated by the markers D1S436 and D1S2843, with a maximum multipoint lod score of 3.6.

Epidemiology of multiple sclerosis in Arabs in Jordan: a comparative study between Jordanians and Palestinians.

In a 2-year hospital-based study in Jordan 131 Arab multiple sclerosis patients were identified including 84 Palestinians and 36 Jordanians. Based on MS/ALS case ratio, multiple sclerosis was found to be twice as common among Palestinians than Jordanians. Other than the less marked female preponderance among Jordanian patients, the disease had the same clinical and paraclinical characteristics in both groups. It was more likely for Palestinian and Jordanian patients to originate from the northern parts of their countries, to be Rh negative and to be HLA-DR2 positive than their controls. Palestinians (patients and controls) did not show significant differences from Jordanians (patients and controls) in relation to their eye color, ABO and Rh blood groups distribution nor the HLA-DR or HLA-DQ (apart from HLA-DQ3) epitopes frequency, thus not offering any significant difference in the genetic-racial markers studies to explain the difference in the observed disease susceptibility. Previous studies demonstrated that 2 racially different populations sharing the same environment can have different risk of developing multiple sclerosis, but this study has shown that this can also be true for 2 racially similar populations sharing the same environment.

Multiple sclerosis in Arabs in Jordan.

In a 2-year hospital-based study (1992 and 1993), there were 131 multiple sclerosis patients attending 2 large referral hospitals in Jordan. Based on MS/ALS case ratios an overall rate of 32.1 (95% CI 19.7-55.2) was estimated. There were 126 Arabs of whom 84 were Palestinians and 36 indigenous Jordanians. Comparison of these subgroups, which had a similar age distribution revealed that the disease was twice as frequent in Palestinians (estimated 42.0/100,000 (CI 2.8-90.8)) among Jordanians (estimated 20.0/100,000 (CI 9.5-47.2)). Clinical presentation, pattern of disease, disability and HLA association were similar to that in the disease reported in Caucasians in the West. All investigations including neurophysiology and imaging were also very similar to Western reports.

Risk factors of aseptic intracranial venous occlusive disease.

INTRODUCTION: Risk factors for aseptic intracranial venous occlusive disease are varied but only few epidemiologic studies were performed to verify the relative importance of particular factors. PATIENTS AND METHODS: A 2-year hospital-based prospective study was conducted in two hospitals to identify the clinical characteristics and risk factors of patients with confirmed aseptic intracranial venous occlusive disease. RESULTS: 21 patients were identified, representing 0.9% of the total neurological admissions. Men were more commonly affected than women; 81% of the patients presented in a clinical picture indistinguishable from idiopathic intracranial hypertension. Risk factors included Behçet's disease in 4, the puerperium in 3, thrombophelia in 3, familial Mediterranean fever in 2, malignancies in 1, lupus anticoagulant in 1, and the contraceptive pill in 1. CONCLUSION: Aseptic intracranial venous occlusive disease proved to be not rare in Arabs. It should be considered seriously in the differential diagnosis of idiopathic intracranial hypertension, particularly in males. Several risk factors were incriminated.

Autosomal recessive ataxia, slow eye movements and psychomotor retardation.

Two consanguineous Arab families with an autosomal recessive form of hereditary ataxia with slow eye movements and psychomotor retardation are reported. The ataxia presented in the first decade, was severely disabling and was associated with a spectrum of eye movements abnormalities as well as psychomotor retardation and sensory neuropathy. MRI studies of the brain showed a significant degree of cerebellar and brainstem atrophy. These 2 families support a previous report of a similarly affected consanguineous Arab family. The syndrome of autosomal recessive ataxia and slow or even absent saccades is proposed to be related but not identical to the autosomal dominant form known as the Wadia Swami syndrome, both of which seem to be related to the olivopontocerebellar degenerations.

Pallido-pyramidal degeneration, supranuclear upgaze paresis and dementia: Kufor-Rakeb syndrome.

An unusual neurological syndrome in an Arab family with five affected siblings, is reported. Autosomal recessive inheritance is suggested by having multiple affected siblings born to phenotypically normal consanguineous parents. Similar to Davison's Pallido-pyramidal syndrome, they presented with the clinical signs and symptoms of severe parkinsonism as well as evidence of cortico-spinal tract disease. In addition, they had dementia and supranuclear upgaze paresis. MRI studies showed significant atrophy of the globus pallidus and the pyramids, as well as generalized brain atrophy in later stages. Therapy with levodopa resulted in significant improvement in the extrapyramidal dysfunction. We suggest that this probably represents a new syndrome which is closely related but not identical to the pallido-pyramidal syndrome.

Neuro-ophthalmic manifestations of the syndrome of ophthalmoplegia, ataxia and areflexia. Observations on 20 patients.

The neuro-ophthalmological manifestations of 20 patients with the syndrome of ophthalmoplegia, ataxia and areflexia are described. The symmetrical nature of the ophthalmoplegia and the associated cerebellar ataxia point to centrally placed lesions. Several supranuclear, nuclear and internuclear ophthalmological signs are identified. Some of these, like partial sparing of the levator palpebrae and normal downgaze in the presence of severe ophthalmoplegia are noted too frequently to be just unusual signs of peripheral oculomotor dysfunction. Other identified features included upper lid retraction on attempted upgaze and preserved Bell's phenomenon in the presence of paralysis of the latter, as well as several other central ophthalmological signs. These findings contrast with those seen in the Guillain-Barré syndrome and, thus, the syndrome of ophthalmoplegia, ataxia and areflexia is not a mere variant of it.

Ataxia and areflexia in SOAA.

Fifteen patients with the classical syndrome of ophthalmoplegia, ataxia, and tendon areflexia (SOAA) were studied in an attempt to clarify the mechanisms of ataxia and myotatic hyporeflexia. All showed features of cerebellar rather than sensory ataxia. Peripheral nerve conduction studies, including F-waves, were normal in a majority of the patients, as was needle EMG. Low-amplitude compound sensory nerve potentials were seen in four patients only, and mild slowing of sensory conduction velocity in two. Three had abnormal blink reflex studies, suggestive of a central lesion in two, and another two showed a transient delay of N5 peak of brainstem auditory evoked potentials. Somatosensory evoked potentials were normal. Despite clinically depressed or absent tendon jerks, T-waves were elicited at normal latencies. These findings do not support the prevailing view that the neurological abnormalities in SOAA are due to involvement of sensory fibres in the peripheral nerves and dorsal roots. We suggest that lesions scattered in the brainstem tegmentum and in the cerebellar peduncles are responsible for the ataxia and the depressed tendon jerks.

Macrocytosis in multiple sclerosis. A study in 82 de novo Arab patients.

Macrocytosis, without anaemia, was common in 82 de novo multiple sclerosis patients compared with a similar number of age and sex matched controls. This was an early phenomenon in the course of the disease and was not influenced by the age of the patients nor the duration of the disease. None of the patients proved to have pernicious anaemia, yet the similarity in the geographical and sex distribution as well as the similarity in HLA associations of multiple sclerosis and pernicious anaemia may indicate that both diseases are under similar genetic influence.

Epidemiology of multiple sclerosis in Arabs in Kuwait: a comparative study between Kuwaitis and Palestinians.

On December 31, 1988 there were 201 registered multiple sclerosis patients in Kuwait, an overall prevalence rate (PR) of 10.2 per 100,000; among them were 186 Arabs, of whom 72 were Palestinians and 51 Kuwaitis. Comparison of these two subgroups, who had a similar age distribution revealed that the disease was 2 1/2 times more frequent among Palestinians (PR 23.8/100,000) than among Kuwaitis (PR 9.5/100,000). Palestinians also showed significant differences from Kuwaitis in eye color, blood group distribution and HLA-DR and HLA-DQW epitopes frequency. This suggests that genetic rather than environmental factors might be the underlying cause for the high susceptibility to develop MS among Arabs originating from the Eastern Mediterranean basin.