Thrombosis complicating high dose intravenous immunoglobulin: report of three cases and review of the literature.

High dose intravenous immunoglobulin (IVG) is increasingly used in a broad range of immune mediated diseases. Thrombosis was exceptionally reported as a complication of this therapy. We describe three cases of thrombotic complications during or soon after IVIG treatment: myocardial infarction in a man and cerebral infarctions in an elderly man, associated with peripheral ischemia in a woman. In addition we review the published cases in the literature and discuss the possible etiologic factors.

Phenytoin dosage adjustment in Saudi epileptics: utilization of steady-state pharmacokinetic parameters.

We determined the Michaelis-Menten parameters (Vmax and Km) in 271 Saudi epileptic patients having generalized tonic-clonic seizures and who were treated with phenytoin (PHT) using high pressure liquid chromatography (HPLC). The patients comprised 150 (55.4%) males and 121 (44.6%) females, with a mean age of 31.7 years (SD = 18.5). The mean Vmax for subjects less than 16 years of age was 10.35 mg/kg/day (SD = 0.73, range = 3.77-17.01), while for those above 16 years, the mean value was 7.99 mg/kg/day (SD = 0.15, range = 3.68-15.95). The difference was statistically significant (P < 0.001). Vmax was positively correlated with weight (r = 0.953), but negative with age (r = -0.903). Km values ranged from 1.01-20.87 mg/litre. The adult Km mean of 6.52 mg/l (SD = 0.24) was significantly higher than the mean of 4.79 mg/l (SD = 0.40) for pediatric patients (P < 0.01), but Km was correlated neither with age nor with weight. Our results showed no difference between the predicted and observed serum PHT concentrations in both the pediatric and adult patients when the respective age group Km and Vmax values were used to adjust PHT doses. The pediatric cases, however, required 30% more PHT per kilogram of body weight than the adults for the achievement of similar serum concentrations.

Dementia in Saudi Arabia: experience from a university hospital.

OBJECTIVES: To describe the pattern of presentation, the types of dementia and the associated conditions in Saudi patients. MATERIALS AND METHODS: Hospital-based study using DSM-IV and ICD 10 criteria for consensus diagnosis of cases from clinical information and results of investigations. Dementia subtypes were made according to NINCDS-ADRDA, NINDS-AIREN and ICD 10 criteria while CDR was used for severity grading. RESULTS: A total of 77 demented patients (49 males, 28 females) were studied. The hospital frequency was 19.3/100,000 patients. The mean age at presentation was 74.6 years and age at onset was below 65 years in 17 patients. The types of dementia were: Alzheimer's disease (51.9%), vascular dementia (18.2%), mixed cases (15.6%), dementia with Parkinson's disease (7.8%) and treatable dementia (5.2%). Only 3 patients were in the severe clinical stage and infections were important causes of deterioration. CONCLUSION: The hospital frequency appears to be low probably because of the relatively young population. The pattern of dementia with preponderance of AD is similar to that in western countries and intervention directed at the risk factors for stroke could reduce the burden of vascular dementia.

Pattern of presentation of multiple sclerosis in Saudi Arabia: analysis based on clinical and paraclinical features.

We studied 89 MS patients comprising 38 males and 51 females seen over a 10-year period. The hospital frequency was 25/100,000 patients. The diagnosis was mainly clinical and was supported by neuroimaging, cerebrospinal fluid analysis and neurophysiological tests. Sixty-five patients (73%) were Saudis and the peak age of onset was in the third decade. Fifty-two patients (58.4%) had clinically definite MS, 17 (19.1%) had laboratory-supported definite MS, 15 (16.9%) were clinically probable MS cases and the remaining 5 (5.6%) had laboratory-supported probable MS. The mean age at onset of Saudi patients (25.9 years) was lower than that of the non-Saudis (29.4 years; p < 0.001). Involvement of the pyramidal system was the commonest mode of presentation. The clinical course was relapsing-remitting in 60.7%, progressive-relapsing in 20.2% and primary progressive in 19.1%. The number of systems involved was significantly associated with the duration of disease (p < 0.001). The demographic features and the variability of clinical presentation of Saudi MS patients is similar to the results from neighbouring countries. Combination of clinical features and paraclinical tests is essential for accurate determination of extent of dissemination and for unmasking clinically silent lesions.

Evolution of brain tuberculomas under standard antituberculous treatment.

The treatment of brain tuberculomas is primarily medical. Surgery, excision or biopsy, is generally performed when the diagnosis is in doubt or there is no response to medical therapy. The aim of this study was to determine the radiological evolution of intracranial tuberculomas under standard anti-tuberculous drug therapy and to establish guidelines for better management of these patients. Eighteen patients were studied retrospectively. None of them had surgical intervention and all were treated by standard antituberculous drugs and had serial computed tomography (CT) scans until disappearance or stabilization of brain lesions. The regression of lesions' size and number was slow in the first month (mean -7.3%) then became rapid after this (-15% to -20% per month). A paradoxical increase in size was noted in three patients in the first month. All three had associated meningitis. All tuberculomas disappeared on CT scan after 12 months of therapy. Most of the edema images disappeared by 6 months. This study would suggest that a long treatment regimen of 15-18 months may not be necessary in most intracranial tuberculomas occurring in non-immunocompromised patients. It also demonstrates that medical trial in well tolerated suspected cases should last for at least 2 months before considering other etiologies or surgical exploration.

Anticardiolipin antibodies as an independent risk factor for stroke in young Saudis.

The role of the anticardiolipin (aCL) antibodies as a predisposing factor for cerebral ischemia in young Saudi patients was investigated in a total of 61 cases (41 males, 20 females; mean age: 34 years). Ten patients had aCL antibodies which were predominantly of the IgG isotype. The mean age and sex ratio of the aCL-positive and aCL-negative cases were similar. The aCL-positive cases had significantly higher frequency of anti-DNA antibodies, lower frequency of HDL, and more prior stroke events and transient ischemic attacks than the aCL-negative cases (p < 0.05) on univariate analysis. However, with multivariate logistic regression analysis, only anti-DNA antibodies and HDL were significantly associated with aCL. Anticardiolipin antibodies represent an independent risk factor for stroke in young Saudi patients and aCL assessment should be considered in young patients with recurrent cerebral ischemia.

Epilepsy classification and factors associated with control in Saudi adult patients.

There is insufficient information on the epilepsies in Saudi Arabia. The objectives were to classify the patients according to seizure types and epilepsies as well as to determine the factors associated with control. In a hospital-based study, clinical information, electroencephalographic and neuroimaging findings were utilized to classify the cases into seizure types and epilepsies according to ILAE criteria and to determine the factors statistically associated with control. In the study there were 826 patients (454 males and 372 females; mean age = 28.7 years; >80% below 30 years at onset). The seizure types were: generalized tonic-clonic (43.8%), partial seizure secondarily generalized (41.9%), myoclonic (8.4%), simple partial (1.3%), complex partial (1.3%) and absence (0.4%). About 15% of the classifiable epilepsies were symptomatic. Most symptomatic epilepsies occurred in people over the age of 50 years. One-year remission rate was 80% and the factors associated with control were: compliance, monotherapy, therapeutic drug level and seizure type. The results showed that epilepsy predominantly affected young adults and confirmed the association of partial epilepsy with clinical and CT abnormalities. The 1-year remission rate was comparable with reports from other studies as well as the factors associated with control in our patients.

Syringomyelia developing as an acute complication of tuberculous meningitis.

BACKGROUND: Tuberculosis of the nervous system has protean manifestations. Syringomyelia, though an uncommon complication of it, is usually of late onset. METHODS: We report two patients with tuberculosis meningitis who developed syringomyelia acutely. The diagnosis was supported by neuroimaging and findings at laminectomy. RESULTS: The two patients developed syringomyelia between 11 days and 6 weeks of the onset of tuberculous meningitis. They both had cord swelling and softening. CONCLUSIONS: Acute-onset syringomyelia should be suspected in any patient being treated for tuberculosis meningitis who subsequently develops limb weakness and/or sphincteric dysfunction. Inflammatory edema and cord ischemia appeared to be the underlying mechanisms in these early onset cases rather than arachnoiditis which is important in late-onset cases.

Deep cerebral venous thrombosis presenting as acute amnestic syndrome.

A 45 year-old man presented with a rapid onset of memory impairment Brain computed tomography showed multiple abnormal low density areas in the deep cerebral white matter. Magnetic resonance imaging revealed bilateral thalamic infarcts and extensive thrombosis of the vein of Galen and the straight sinus, which was confirmed by cerebral angiography. The only potential cause was protein S deficiency. Heparin therapy was started only after the occurrence of a pulmonary embolism. The outcome was excellent Deep cerebral venous thrombosis must be considered as a possible cause of amnestic syndrome. Clinical awareness and early use of anticoagulation may alter the usual fatal outcome.

Is HLA-DRW13 (W6) associated with juvenile myoclonic epilepsy in Arab patients?

In a study of 32 unrelated Arab patients with juvenile myoclonic epilepsy (JME), we compared the frequencies of human leukocyte antigen (HLA) class I and II alleles with those of unrelated healthy controls. A significant difference between the phenotypic frequencies in JME patients and controls was observed for DRW13, the split of DRW6 (37.5 vs 11% of controls). The strength of association as measured by the relative risk was 4.85 for this antigen (p = 0.002). The possible association of JME with HLA-DRW6 recently reported in Caucasians was confirmed in this study. This finding speaks for the homogeneity of the disease among Arabic and Caucasian JME patients. The existence of this association is evidence of a locus in the HLA region that influences expression of JME.

Significant elevation of protein C and protein S levels in thrombotic disorders by low dose danazol.

Six patients (three males and three females), mean age 35.2 years (range 31-43 years), with extensive venous thrombosis were studied. Initial laboratory data indicated that all patients had normal antithrombin III (ATIII), four patients had low protein C (PC), three patients had low protein S (PS) and two patients had low plasminogen. Four patients had high fibrinogen and all patients had reduced tissue-type plasminogen activator activity, elevated tissue plasminogen activator inhibitor and low fibrinolytic activity. All patients were treated with danazol, 5-7 mg/kg orally once daily. In all patients there was significant elevation of ATIII, PC, PS, and plasminogen, reduction in plasma fibrinogen and PAI and enhancement of fibrinolysis. During the 12-36 months period of follow-up, there were no symptoms or signs that suggested recurrence of thrombosis. Apart from weight gain of 5-10 kg and disturbed menstrual cycle in two women, no major side effects were seen. These data suggest that danazol is potentially useful therapy that may increase levels of natural anticoagulants in patients with thrombotic illnesses in which ATIII, PC and PS are low or normal. Further studies are needed to confirm these observations.

The value of oligoclonal bands in neurobrucellosis.

We performed polyacrylamide gel isolectric focusing on diluted sera and non-concentrated CSF from ten patients with neurobrucellosis, ten patients with definite multiple sclerosis, seven patients with neuro-Behcet's syndrome, five patients with tuberculous meningitis, and eight patients with other neurological disorders. Our data support the proposed theory of the intrathecal synthesis of immunoglobulins in the presence of neurobrucellosis, and showed that evidence of oligoclonal IgG bands in cerebrospinal fluid and serum provides rapid and helpful confirmation of diagnosis of neurobrucellosis.

Photosensitive epilepsies and photoconvulsive responses in Arabs.

The occurrence of photosensitivity (PS) was examined in 327 Arabs greater than or equal to 15 years of age with epilepsy by intermittent photic stimulation (IPS). A control group of 192 nonepileptic Arabs greater than or equal to 15 years of age were also examined by IPS. Of the epileptic patients, 24 (7.3%) were photosensitive, an incidence comparable to that in whites in contradistinction to the reported rarity among African blacks. This finding indicates that environmental factors, particularly excessive sunshine, does not appear to influence the occurrence of PS among epileptic patients. The occurrence of PS among epileptic patients may depend more strongly on the presence of an epileptic syndrome known to have association with PS.

Bickerstaff brainstem encephalitis. A grave non-demyelinating disease with benign prognosis.

We describe 6 patients with ophthalmoplegia, ataxia and normal or exaggerated deep tendon reflexes. All had been preceded by a febrile illness and had a full recovery without sequelae. The brainstem auditory evoked potentials showed a localised lesion in the upper brainstem while the pattern shift visual evoked potentials were normal and did not show any additional silent lesions. CSF IgG oligoclonal bands were not detected in any of the patients. MRI in 2 patients showed a confluent high intensity lesion in the upper mesencephalon and thalamus involving white and gray matter. Follow-up ranged from 6 to 24 months and showed no relapse.

Successful treatment of cherry red spot-myoclonus syndrome with 5-hydroxytryptophan.

A 14-year-old Saudi boy with cherry red spot-myoclonus syndrome and documented neuraminidase deficiency responded well to titrated doses of 5-hydroxytryptophan as an add-on treatment.

Neurological syndromes of brucellosis.

Eleven patients with brucellosis presented with neurological features closely simulating transient ischaemic attacks, cerebral infarction, acute confusional state, motor neuron disease, progressive multisystem degeneration, polyradiculoneuropathy, neuralgic amyotrophy, sciatica and cauda equina syndrome. Most patients improved quickly after adequate antibiotic treatment but chronic cases responded poorly. These protean neurological manifestations of brucellosis indicate that the underlying pathological mechanisms are diverse.