Guillaume Taieb

Long-term Outcomes of CLIPPERS (Chronic Lymphocytic Inflammation With Pontine Perivascular Enhancement Responsive to Steroids) in a Consecutive Series of 12 Patients

BACKGROUND Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory disease. OBJECTIVE To describe the disease course of CLIPPERS. DESIGN A nationwide study was implemented to collect clinical, magnetic resonance imaging, cerebrospinal fluid, and brain biopsy specimen characteristics of patients with CLIPPERS. SETTING Academic research. PATIENTS Twelve patients with CLIPPERS. MAIN OUTCOME MEASURES The therapeutic management of CLIPPERS was evaluated. RESULTS Among 12 patients, 42 relapses were analyzed. Relapses lasted a mean duration of 2.5 months, manifested frequent cerebellar ataxia and diplopia, and were associated with a mean Expanded Disability Status Scale (EDSS) score of 4. Besides typical findings of CLIPPERS, magnetic resonance imaging showed brainstem mass effect in 5 patients, extensive myelitis in 3 patients, and closed ring enhancement in 1 patient. Inconstant oligoclonal bands were found on cerebrospinal fluid investigation in 4 patients, with an increased T-cell ratio of CD4 to CD8. Among 7 available brain biopsy specimens, staining was positive for perivascular CD4 T lymphocytes in 5 samples. Thirty-eight of 42 relapses were treated with pulse corticosteroid therapy, which led to improvement, with a mean residual EDSS score of 1.9 (range, 0-7). In 1 patient with untreated relapses, scores on the EDSS progressively increased to a score of 10 at death. Among 5 patients without long-term corticosteroid therapy, the mean annualized relapse rate was 0.5 (range, 0.25-2.8). Among 7 patients taking oral corticosteroids, no relapses occurred in those whose daily dose was 20 mg or higher. No progressive course of CLIPPERS was observed. Four patients with a final EDSS score of 4 or higher had experienced previous severe relapses (EDSS score, ≥5) and brainstem and spinal cord atrophy. CONCLUSIONS CLIPPERS is a relapsing-remitting disorder without progressive forms. Long-term disability is correlated with the severity of previous relapses. Further studies are needed to confirm that prolonged corticosteroid therapy prevents further relapses.

Cannabis-Related Myocardial Infarction and Cardioembolic Stroke

We report a 33-year-old man with a history of chronic cannabis use who sustained myocardial infarction followed by cerebral infarction after a recent significant increase in cannabis use. This is the first case of cannabis-associated stroke of probable cardioembolic origin.

Sensory chronic inflammatory demyelinating polyneuropathy: An under‐recognized entity?

Sensory chronic inflammatory demyelinating polyneuropathy (CIDP) can be difficult to diagnose.

Autoantibodies to nodal isoforms of neurofascin in chronic inflammatory demyelinating polyneuropathy

Chronic inflammatory demyelination polyneuropathy is a heterogeneous and treatable immune-mediated disorder that lacks biomarkers to support diagnosis. Recent evidence indicates that paranodal proteins (contactin 1, contactin-associated protein 1, and neurofascin-155) are the targets of autoantibodies in subsets of patients showing distinct clinical presentations. Here, we identified neurofascin-186 and neurofascin-140 as the main targets of autoantibodies in five patients presenting IgG reactivity against the nodes of Ranvier. Four patients displayed predominantly IgG4 antibodies, and one patient presented IgG3 antibodies that activated the complement pathway in vitro. These patients present distinct clinical features compared to those with anti-neurofascin-155 IgG4. Most patients had a severe phenotype associated with conduction block or decreased distal motor amplitude. Four patients had a subacute-onset and sensory ataxia. Two patients presented with nephrotic syndromes and one patient with an IgG4-related retroperitoneal fibrosis. Intravenous immunoglobulin and corticosteroids were effective in three patients, and one patient remitted following rituximab treatment. Clinical remission was associated with autoantibody depletion and with recovery of conduction block and distal motor amplitude suggesting a nodo-paranodopathy. Our data demonstrate that the pathogenic mechanisms responsible for chronic inflammatory demyelination polyneuropathy are broad and may include dysfunctions at the nodes of Ranvier in a subgroup of patients.

A new case of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids with initial normal magnetic resonance imaging

Sir, We read with great interest the recent article published in Brain by Pittock et al. (2010), who reported eight patients with clinical, radiological and pathological features of brainstem involvement responsive (but dependent) to steroid treatment. All the reported patients shared common clinical and MRI findings: gait ataxia, diplopia, patchy increased T2 signal and gadolinium enhancement within the pons and the middle cerebellar peduncles, the presence of oligoclonal bands on CSF analysis, and normal cerebral angiography. Involvement of the medulla, the cerebellum, the midbrain, the basal ganglia, the corpus callosum and the spinal cord has also been described. Brain biopsy of four patients found white matter T-lymphocytic infiltrate with perivascular predominance. Steroids led to clinical and neuroradiological improvement in all patients, with steroid dependency in three (mean follow-up: 22 months, range: 7–144 months). CLIPPERS (acronym for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) was proposed to …

An MRI review of acquired corpus callosum lesions

Lesions of the corpus callosum (CC) are seen in a multitude of disorders including vascular diseases, metabolic disorders, tumours, demyelinating diseases, trauma and infections. In some diseases, CC involvement is typical and sometimes isolated, while in other diseases CC lesions are seen only occasionally in the presence of other typical extra-callosal abnormalities. In this review, we will mainly discuss the MRI characteristics of acquired lesions involving the CC. Identification of the origin of the CC lesion depends on the exact localisation of the lesion(s) inside the CC, presence of other lesions seen outside the CC, signal changes on different MRI sequences, evolution over time of the radiological abnormalities, history and clinical state of the patient, and other radiological and non-radiological examinations.

Neurofascin-155 as a putative antigen in combined central and peripheral demyelination

Combined central and peripheral demyelination (CCPD) encompasses a wide array of disorders ranging from myeloradiculoneuritis and encephalomyeloradiculoneuritis, which often occur after infection or vaccination, to co-occurrence of multiple sclerosis (MS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).1,2

Thalamic Lesions: A Radiological Review

Background. Thalamic lesions are seen in a multitude of disorders including vascular diseases, metabolic disorders, inflammatory diseases, trauma, tumours, and infections. In some diseases, thalamic involvement is typical and sometimes isolated, while in other diseases thalamic lesions are observed only occasionally (often in the presence of other typical extrathalamic lesions). Summary. In this review, we will mainly discuss the MRI characteristics of thalamic lesions. Identification of the origin of the thalamic lesion depends on the exact localisation inside the thalamus, the presence of extrathalamic lesions, the signal changes on different MRI sequences, the evolution of the radiological abnormalities over time, the history and clinical state of the patient, and other radiological and nonradiological examinations.

Punctate and curvilinear gadolinium enhancing lesions in the brain: a practical approach.

IntroductionCerebral punctate and curvilinear gadolinium enhancements (PCGE) correspond to opacification of small vessel lumen or its perivascular areas in case of blood-brain barrier (BBB) disruption. We will discuss the possible causes of intra-parenchymal central nervous system PCGE.MethodsOur review is based on French database including patients presenting with central nervous system PCGE and literature search using PubMed database with the following keywords: punctate enhancement, linear enhancement, and curvilinear enhancement. Disorders which displayed linear leptomeningeal or periventricular enhancements without intra-parenchymal PCGE are excluded of this review.ResultsAmong our 39 patients with PCGE, 16 different diagnoses were established. After combining our PCGE causes with those described in the literature, we propose a practical approach. Besides physiologic post-contrast enhancement of small vessels, three pathologic conditions may exhibit PCGE: (1) small collateral artery network seen in Moyamoya syndrome, (2) small veins congestions related to developmental or acquired venous outflow disturbance, and (3) disorders causing small vessels BBB disruption indicated by T2 and FLAIR hyperintensities in the corresponding areas of PCGE. Disruption of the BBB could be caused by a direct injury of the endothelial cell, as in posterior reversible encephalopathy syndrome, Susac syndrome, and radiochemotherapy-induced injuries, or by an angiocentric cellular infiltrate, as in inflammatory disorders, demyelinating diseases, host immune responses fighting against infections, prelymphoma states, lymphoma, and in CLIPPERS.ConclusionPCGE may conceal several causes, including physiological and pathological conditions. Nevertheless, a practical approach could improve its management and limit the indications of brain biopsy to very specific situations.

Neurological picture. Cortical susceptibility-weighted imaging hypointensity after stroke-like episode in MELAS.

A 49-year-old woman with a known m.3243A>G tRNALeu(UUR) mutation (ie, the most frequent mutation in mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS)) diagnosed in the presence of migraine, diabetes mellitus, neurosensory hearing loss, short stature, cognitive deficit, ataxia and elevated lactate levels, presented with subacute aphasia and right hemiplegia. Brain MRI showed a typical stroke-like lesion in the left temporal and parietal lobe and prerolandic cortex. At this time, gradient-echo T2-weighted imaging showed hyperintensities in the involved regions (also visible on T2-weighted and FLAIR imaging, probably due to the …