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

BACKGROUND: 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). METHODS: A retrospective, observational study was carried out. All patients (n=45) initiated natalizumab after experiencing at least 1 relapse in the previous year under interferon-beta (IFNB) or glatiramer acetate (GA) treatments. The patients also had at least 1 gadolinium-enhancing (Gd+) lesion on their baseline brain MRI. Expanded Disability Status Scale (EDSS) scores, and performance on the Timed 25-Foot Walk Test and on the Timed 100-Metre Walk Test were prospectively collected every 4 weeks during 44 weeks of natalizumab treatment. Brain MRI scans were performed after 20 and 44 weeks of treatment. RESULTS: Sixty-two per cent of patients showed no clinical and no radiological signs of disease activity, and 29% showed a rapid and confirmed EDSS improvement over 44 weeks of natalizumab therapy. Patients with improvement on the EDSS showed similar levels of baseline EDSS and active T1 lesions, but had a significantly higher number of relapses, and 92% of them had experienced relapse-mediated sustained EDSS worsening in the previous year. A clinically meaningful improvement in ambulation speed was observed in approximately 30% of patients. CONCLUSIONS: These results indicate that natalizumab silences disease activity and rapidly improves disability status and walking performance, possibly through delayed relapse recovery in patients with RRMS who had shown a high level of disease activity under other DMTs.

[Misdiagnosis of sinus thrombosis with reversible posterior leucoencephalopathy]. / Thrombose ou hypoplasie veineuse cérébrale avec leucoencéphalopathie postérieure réversible.

Reversible posterior leucoencephalopathy and cerebral venous thrombosis share many symptoms. Both of them may lead to coma, and cause epilepsy or focal neurological signs. Moreover, diffuse leucoencephalopathy can be observed in both cases. Cerebral venous thrombosis needs anticoagulation which is not a riskless treatment. We describe a case of reversible posterior leucoencephalopathy in an hypertensed, seventy-year old man, presenting with a left lateral sinus hypoplasia whose clinical history and paramedical results first suggested a cerebral veinous thrombosis. Our case shows the misleadings a congenital vascular asymmetry can induce when confronted with a subacute coma.

The French Addenbrooke's cognitive examination is effective in detecting dementia in a French-speaking population.

We evaluated the sensitivity and specificity of our French version of Addenbrooke's cognitive examination (ACE) to detect dementia in our patient population. One hundred and fifty-eight cases were included in the study. In our patient series, the sensitivity for diagnosing dementia with a Mini-Mental State Examination (MMSE) score of < or = 24/30 was 48.5%, the sensitivity of an MMSE score of < or = 27/30 was 82.5% with a specificity of 72.1%, the sensitivity of an ACE score of < or = 83/100 was 86.6% with a specificity of 70.5% and the sensitivity of an ACE score of < or = 88/100 was 97.9% with a specificity of 59%. We conclude that the French version of the ACE is a very accurate test for the detection of dementia, and should be widely used in clinical practice.

Is the Addenbrooke's cognitive examination effective to detect frontotemporal dementia?

We evaluated the Addenbrooke's cognitive examination (ACE), a simple instrument to differentiate frontotemporal dementia (FTD) from Alzheimer's disease (AD), in our dementia patients clinic population. The Verbal-Language/Orientation-Memory (VLOM) ratio, which compares its language and memory scores, determines whether FTD or AD is more likely. The ACE was translated into French with adaptation maintaining the number of words in the name and address learning and delayed recall test, and with cultural adaptation for the semantic memory. The 85 included subjects had no evidence of two or more organic pathologies, after at least six months of follow-up, and an MMSE score>or=20/30. Patients with cognitive impairment due to alcohol intake were excluded. The diagnosis of a specific dementing illness was based on the consensus of the neurologist and neuropsychologists in the team. Thereafter, another neurologist expert in dementia, blinded to the ACE result and to the diagnosis and treatment, reviewed all cases files and proposed a diagnosis. A diagnostic agreement was reached for 79 cases (92.9%) with 40 (50.6%) dementia: 25 AD (62.5 %), 9 FTD (22.5 %). We estimated that the sensitivity for detecting dementia of an ACE score3.2 was 72%,with a specificity of 69.4%. We conclude that, when used as originally proposed, ACE is very accurate for the detection of dementia, but much less effective in discriminating the most common frontal variant of FTD.

Could visual neglect induce amblyopia?

Oculomotor nerve disease is a common cause of diplopia. When strabismus is present, absence of diplopia has to induce the research of either uncovering of visual fields or monocular suppression, amblyopia or blindness. We describe the case of a 41-year-old woman presenting with right oculomotor paresis and left object-centred visual neglect due to a right fronto-parietal haemorrhage expanding to the right peri-mesencephalic cisterna caused by the rupture of a right middle cerebral artery aneurysm. She never complained of diplopia despite binocular vision and progressive recovery of strabismus, excluding uncovering of visual fields. Since all other causes were excluded in this case, we hypothesise that the absence of diplopia was due to the object-centred visual neglect. Partial internal right oculomotor paresis causes an ocular deviation in abduction; the image being perceived deviated contralaterally to the left. Thus, in our case, the neglect of the left image is equivalent to a right monocular functional blindness. However, bell cancellation test clearly worsened when assessed in left monocular vision confirming that eye patching can worsen attentional visual neglect. In conclusion, our case argues for the possibility of a functional monocular blindness induced by visual neglect. We think that in presence of strabismus, absence of diplopia should induce the search for hemispatial visual neglect when supratentorial lesions are suspected.

Antiphospholipid antibodies and ischemic neuropathy following cardiac surgery.

Sciatic nerve palsy is an uncommon complication of cardiac surgery and is thought to be induced by a combination of reduced femoral artery blood flow, small vessel vascular disease or prolonged hypoxia. We here describe a new case which is the first described with transient elevation of antiphospholipid antibodies. Although transient elevation of lupus coagulation inhibitor is known to occur frequently in patients treated in an intensive care unit, there are very few data about the possible role of antiphospholipid antibodies in the generation of ischemic neuropathies. We can not prove that the ischemic neuropathy in our case has been favored by the presence of lupus coagulation inhibitor and antiphospholipid antibodies as the occurrence of the symptoms seemed to precede the transient elevation of lupus coagulation inhibitor. This case suggests that antiphospholipid antibodies and lupus coagulation inhibitor should be included in the work up of patients who present nerve damage after cardiac surgery but further studies are needed to ascertain this association.

Effects of levodopa on upper limb mobility and gait in Parkinson's disease.

BACKGROUND: Most clinicians rely on clinical scales such as the unified Parkinson's disease rating scale (UDPRS) for evaluating parkinsonian patients and assessing their response to levodopa. Gait analysis is not commonly used, probably because of the equipment required and the time needed. Few data have been published on the relations between gait variables and measures of arm and hand mobility. OBJECTIVES: To evaluate the correlation between dopa induced gait improvement and upper limb motor improvement using a rapid and simple method; and to evaluate the correlation between gait improvement and UPDRS III improvement. METHODS: A finger tapping test and a simple walking test were used to measure the OFF-ON variations of upper limb motor function and gait in 23 patients with Parkinson's disease. The UPDRS motor score and the Hoehn and Yahr stage were measured in the OFF and the ON state. RESULTS: There was no correlation between OFF-ON variation of the number of hits with the finger tapping test and OFF-ON variation in the gait variables. OFF-ON variation in the UPDRS motor score was not correlated with OFF-ON variation in the gait variables. CONCLUSIONS: There was a dissociation between the effect of levodopa on upper limb and gait. The findings suggest that simple measures like the finger tapping test and a walking test should be included in the usual evaluation of patients with Parkinson's disease.

The cerebellum may be directly involved in cognitive functions.

Neuropsychological deficits may occur in infratentorial strokes. Only minor cognitive disturbances are reported in unilateral anterior cerebellar lesions. Here, the authors describe a patient with bilateral anterior ponto-cerebellar ischemic lesions associated with major neuropsychological deficits. Cerebral PET and SPECT demonstrated no metabolic defect in supratentorial areas.