Emmanuel Bartholomé

Stroke Presentation and Outcome in Developing Countries A Prospective Study in The Gambia

Background and Purpose— Despite increasing burden of stroke in Africa, prospective descriptive data are rare. Our objective was to describe, in The Gambia, the clinical outcome of stroke patients admitted to the Royal Victoria Teaching Hospital in the capital Banjul, to assess mortality and morbidity, and propose preventive and therapeutic measures. Methods— Prospective data were collected on consecutive patients older than 15 years old admitted between February 2000 and February 2001 with the diagnosis of nonsubarachnoid stroke. Risk factors, clinical characteristics, and social consequences were assessed using a modified National Institutes of Health Stroke Scale (mNIHSS), the Barthel Activity in Daily Living scale, the Siriraj score for subtypes, and the Bamford criteria for location/extension. Patients were followed-up at home up to 1 year after discharge. Results— Ninety-one percent (148/162) of eligible patients were enrolled and followed-up. Hypertension and smoking were the most prevalent risk factors. Severity was high at admission, especially in women, and was strongly correlated to the outcome. mNIHSS and consciousness level on admission were strong predictors of the mortality risk. Swallowing difficulties at admission, fever, lung infection, and no aspirin treatment were, independently, risk factors for a lethal outcome susceptible to being addressed by treatment. Mortality was 41% in-hospital and 62% after 1 year. In survivors, autonomy levels improved over time. Drug compliance was poor. At home, family members provided care. Long-term socioeconomic and cultural activities were affected in most patients. Conclusions— Case-fatality was high compared with Western cohorts. Preventive measures can be developed. Rational treatment, in the absence of head imaging for initial assessment, requires adapted protocols. Providers should be trained, both at hospital and community levels.

Natalizumab induces a rapid improvement of disability status and ambulation after failure of previous therapy in relapsing-remitting multiple sclerosis.

Background:u2002 Natalizumab (Tysabri) is a monoclonal antibody that was recently approved for the treatment of relapsing‐remitting multiple sclerosis (RRMS). Our primary objective was to analyse the efficacy of natalizumab on disability status and ambulation after switching patients with RRMS from other disease‐modifying treatments (DMTs).

Safety and efficacy of natalizumab in Belgian multiple sclerosis patients: subgroup analysis of the natalizumab observational program

Natalizumab (Tysabri®) is highly efficacious in controlling disease activity in relapsing multiple sclerosis (MS) patients. As it is one of the more recent therapies for MS, there remains a need for long-term safety and efficacy data of natalizumab in a clinical practice setting. The Tysabri observational program (TOP) is an open-label, multicenter, multinational, prospective observational study, aiming to recruit up to 6,000 patients with relapsing-remitting MS from Europe, Canada and Australia. The objectives of this study are to collect long-term safety and efficacy data on disease activity and disability progression. We report here the interim results of the 563 patients included in TOP between December 2007 and 2012 from Belgium. This patient cohort was older at baseline, had longer disease duration, higher neurological impairment, and a higher baseline annualized relapse rate, when compared to patients included in the pivotal phase III AFFIRM trial. Nevertheless, the efficacy of natalizumab was comparable. The annualized relapse rate on treatment was reduced by 90.70xa0% (pxa0<xa00.0001) with a cumulative probability of relapse of 26.87xa0% at 24xa0months. The cumulative probabilities of sustained disability improvement and progression at 24xa0months were 25.68 and 9.01xa0%, respectively. There were no new safety concerns over the follow-up period. Two cases of progressive multifocal leukoencephalopathy were diagnosed. Our results are consistent with other observational studies in the post-marketing setting.

Striatal lesions: an underestimated complication of cerebral malaria?

Sirs, Cerebral malaria (CM) is characterized by altered consciousness, acute confusional state, seizures, anaemia, hypoglycaemia, brainstem involvement and retinal haemorrhage with confirmation of Plasmodium parasitaemia, when other causes of encephalopathy have been excluded. (Nguyen et al., 1996; Newton andWarrell, 1998) Brain imaging in CM typically shows an increase in brain volumewith or without cerebral oedema whereas focal cerebral lesions are usually not present (Newtonand Warrell, 1998). We here report the first description of CM complicated by bilateral striatal lesions and propose a possible physiopathological mechanism. A37-year-old right-handedBelgianman presented with fever (40 C), diarrhoea, hypotension (71/43 mmHg) and anuric renal failure 5 days after his return from Kenya where he had not taken any antimalarial prophylactic therapy. His medical history was unremarkable. Peripheral blood smear was positive for Plasmodium falciparum (40% parasitaemia). Plasma lactate was >8 mEq/l with a pH of 7, 18. Treatment by quinine 1.5 g/day was initiated. He then presented generalized tonic-clonic seizures. Brain magnetic resonance imaging showed bilateral lesions affecting globus pallidus, subthalamic nucleus and substantia nigra (Fig. 1). When he was admitted in our rehabilitation unit 2 months later, he suffered from tetraparesis and parkinsonism. Neurological examination revealed saccadic pursuit and several extrapyramidal signs including bilateral upper limbs rigidity, postural tremor and bradykinesia, a tetraparesis predominantly affecting the lower limbs with bilateral lower limb hyporeflexia. There were no pyramidal or cerebellar signs. Electrophysiological investigations disclosed an ongoing axonal sensorimotor polyneuropathy suggesting intensive care unit polyneuropathy. Striatal lesions have never been described as a complication of CM. The identified causes of bilateral striatal necrosis are severe metabolic acidosis, methanol intoxication, carbon monoxide intoxication, hypoxic encephalopathy, cyanide poisoning, venous infarction, osmotic demyelination, Wilson’s disease, Leigh’s syndrome, mitochondrial encephalopathy, haemolytic-uraemic syndrome, sickle-cell disease acidosis, metformin-induced lactic acidosis,Mycoplasma pneumoniae infection, Arthrinium-produced mycotoxin, glutaric acidemia and rare cases of familial striatal necrosis (Goodman and Norenberg, 1983; He et al., 1995; Kamei et al., 1996; Mewborne et al., 1998; Faris et al., 2000; Zambrino et al., 2000). In most of these cases, the implicated pathogenic mechanism is thought to be a preferential sensibility of striatal neurons to lactic acidosis induced by disturbance of the mitochondrial metabolism (Kamei et al., 1996). Compared with these cases, our patient presented bilateral lesions of the striatum and parkinsonism almost disappeared after 1 year of follow-up. Interestingly, there are only few descriptions of extrapyramidal syndrome associated with CM (Arya et al., 1989; Chaudhary et al., 1992) or following chloroquine therapy (Singhiet al., 1979). In these cases, neither focal brain lesion were reported nor physiopathological mechanism proposed (Singhi et al., 1979; Arya et al., 1989; Chaudhary et al., 1992). However, mild parkinsonism because of striatal lesions may have been underestimated in developing countries where CM is more frequent. In our case the co-occurrence of CM, lactic acidosis and systemic hypotensionmay explain the severity of the clinicalradiological picture (Kamei et al., 1996). In conclusion, clinicians should be aware that CMmay cause striatal lesions and should systematically search for extrapyramidal signs in patients with CM and lactic acidosis, especially when systemic hypoxia or hypotension are present.

Thyroid disorders in alemtuzumab-treated multiple sclerosis patients: a Belgian consensus on diagnosis and management

This paper deals with thyroid disease that can occur after treatment with alemtuzumab (humanized monoclonal anti-CD52) for relapsing–remitting multiple sclerosis (MS). The 5-year incidence of thyroid adverse events in phase 3 clinical trials is up to 40.7%. In most cases, the thyroid dysfunction is mild and easily manageable and only few serious thyroid adverse events have been reported. The need for patient education on the risk of thyroid dysfunction, as well as regular clinical and biochemical thyroid function screening is well described. However, practical clinical guidance in case of abnormal thyroid-related findings prior to or after alemtuzumab treatment is currently lacking. Therefore, a Belgian taskforce consisting of MS and thyroid experts was created in 2016, with the objective of issuing a clinical thyroid management algorithm based on available scientific evidence and personal experience with regard to alemtuzumab treatment-related thyroid adverse events.