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Objective: Whole genome sequencing and the screening of 103 families recently led us to identify PRRT2 (proline-rich-transmembrane protein) as the gene causing infantile convulsions (IC) with paroxysmal kinesigenic dyskinesia (PKD) (PKD/IC syndrome, formerly ICCA). There is interfamilial and intrafamilial variability and the patients may have IC or PKD. Association of IC with hemiplegic migraine (HM) has also been reported. In order to explore the mutational and clinical spectra, we analyzed 34 additional families with either typical PKD/IC or PKD/IC with migraine.Methods: We performed Sanger sequencing of all PRRT2 coding exons and of exon-intron boundaries in the probands and in their relatives whenever appropriate.Results: Two known and 2 novel PRRT2 mutations were detected in 18 families. The p.R217Pfs*8 recurrent mutation was found in z50% of typical PKD/IC, and the unreported p.R145Gfs*31 in one more typical family. PRRT2 mutations were also found in PKD/IC with migraine: p.R217Pfs*8 cosegregated with PKD associated with HM in one family, and was also detected in one IC patient having migraine with aura, in related PKD/IC familial patients having migraine without aura, and in one sporadic migraineur with abnormal MRI. Previously reported p.R240X was found in one patient with PKD with migraine without aura. The novel frameshift p.S248Afs*65 was identified in a PKD/IC family member with IC and migraine with aura. Conclusions:We extend the spectrum of PRRT2 mutations and phenotypes to HM and to other types of migraine in the context of PKD/IC, and emphasize the phenotypic pleiotropy seen in patients with PRRT2 mutations. Neurology There is a long known relationship between human epilepsies and other paroxysmal brain disorders, such as migraine, episodic ataxia, or paroxysmal dyskinesia-the occurrence of involuntary movements, whether spontaneous or triggered by various types of stimuli. Evidence for shared pathophysiologic mechanisms underlying the concurrence of benign infantile convulsions (IC) and of paroxysmal kinesigenic dyskinesia (PKD) in the same patients or families was obtained more than 15 years ago.

Background: Since the use of tissue plasminogen activator for acute ischemic stroke (IS), stroke care pathways have been developed for patients with suspicion of acute stroke. The aim of this prospective observational study was to analyze the stroke mimic (SM) characteristics in patients who were part of our stroke care pathway. Methods: All consecutive patients admitted in the code stroke within a 1-year period were prospectively enrolled in this study. Patients with a sudden onset of neurological focal deficit in a time window less than 4H30 as indicated for intravenous thrombolysis, had been accepted in the pathway by a neurologist who was directly contactable by the prehospital emergency medical service 24 h per day. Patients arrived directly on the MRI site without passing by the emergency department. A clinical neurological evaluation and a brain MRI with tri-dimensional time-of-flight magnetic resonance angiography were performed. The FAST score was calculated a posteriori. The final discharge diagnosis was concluded either immediately after both neurological examination and cerebrovascular neuroimaging or after other relevant investigations. We classified the discharge diagnosis into neurovascular diseases (NVDs) and into SM. Results: There were 1,361 consecutive patients admitted for suspicion of acute stroke. Sixty-two percent (n = 840) had an NVD including IS (n = 529), transient ischemic attacks (n = 236), intracranial hemorrhages (n = 68), cerebral venous thrombosis (n = 3) and neurovascular medullar pathologies (n = 4). SM represented 38% of cases (n = 521) and the most frequent discharge diagnosis was defined as headaches (18.6%), psychological disorders (16.7%), peripheral vertigo (11.9%) and epilepsy (10.6%). The comparison between the characteristics of the NVD and those of the SM groups showed some significant differences: in the SM group, women were more represented, patients were younger and the NIHSS was lower than in the NVD group. All cardiovascular risk factors were more represented in the NVD group. Concerning the symptoms, motor deficit, speech disturbances, homonymous lateral hemianopia and head and gaze deviation were more represented in the NVD group, whereas vertigo, non-systematized visual trouble, headache, confusion, weakness, neuropsychological symptoms, seizure and chest pain were significantly more frequent in the SM group. The negative predictive value of the FAST score was 64% and the positive predictive value was 76%. Conclusions: A rate of SM up to 38% of the code stroke system confirms the difficulty to distinguish clinically a stroke from another diagnosis. In this study, using cerebral MRI in first intention was of special interest in patients with acute neurological symptoms to differentiate an NVD from an SM.

Inherited white matter diseases are rare and heterogeneous disorders usually encountered in infancy. Adult-onset forms are increasingly recognized. Our objectives were to determine relative frequencies of genetic leukoencephalopathies in a cohort of adult-onset patients and to evaluate the effectiveness of a systematic diagnostic approach. Inclusion criteria of this retrospective study were: (i) symmetrical involvement of white matter on the first available brain MRI; (ii) age of onset above 16 years. Patients with acquired diseases were excluded. Magnetic resonance imaging analysis identified three groups (vascular, cavitary and non-vascular/non-cavitary) in which distinct genetic and/or biochemical testing were realized. One hundred and fifty-four patients (male/female = 60/94) with adult-onset leukoencephalopathies were identified. Mean age of onset was 38.6 years. In the vascular group, 41/55 patients (75%) finally had a diagnosis [including CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, n = 32) and COL4A1 mutation, n = 7]. In the cavitary group, 13/17 (76%) patients had a diagnosis of EIF2B-related disorder. In the third group (n = 82), a systematic biological screening allowed a diagnosis in 23 patients (28%) and oriented direct genetic screening identified 21 additional diseases (25.6%). Adult-onset genetic leukoencephalopathies are a rare but probably underestimated entity. Our study confirms the use of a magnetic resonance imaging-based classification with a final diagnosis rate of 64% (98/154) cases.

The authors studied a 47-year-old patient who presented with an association of deafness, acute cerebral stroke-like episode, leukoencephalopathy, and extensive basal ganglia calcifications. Late onset and neuroradiologic findings were atypical for MELAS syndrome (Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Strokelike episodes). A heteroplasmic G to A transition at nucleotide 4332 in the tRNA glutamine gene was identified in the patient's muscle mitochondrial DNA. The pathogenicity of the mutation was shown in single muscle fibers by the correlation between high mutation load and cytochrome c oxidase defect.

Background: Given the discordant results of studies that have reported cases of RLS associated with brainstem stroke and the absence of RLS in large series describing the clinical spectrum of brainstem infarctions, we decided to assess RLS in all patients admitted for brainstem stroke. Methods: All patients who were consecutively referred to the Strasbourg stroke unit for brainstem infarction were prospectively evaluated for RLS. The different parameters analyzed were the topography of the ischemic lesions (magnetic resonance imaging), the different symptoms (sensory, motor, cerebellar, cranial nerves and dysarthria) and the NIH stroke scale. Statistical analyses used the Bayesian paradigm. Results: Thirty patients have been included, and RLS was observed in three patients (10%). Two patients suffered from an exacerbation of symptoms anterior to the stroke, and the other patient a de novo, but transient, RLS. Patients with stroke-induced sensory symptoms have a higher risk to develop brainstem stroke-related RLS as compared to patients without sensory symptoms. Conclusion: The results suggest that RLS should be systematically screened in patients affected with brainstem stroke, especially in the case of stroke-induced sensory symptoms. Clinicians should be aware of this association, especially as efficient treatments are available and allow improving the management of patients affected with stroke. i 2014 S. Karger AG, Basel

A 73-year-old man complained at bedtime of "electric shock" sensations, corresponding to myoclonic-like jerks, observed solely in both arms, causing severe insomnia. These involuntary movements appeared at rest and were accompanied by an urge to move that relieved symptoms (video on the Neurology ® Web site at Neurology.org). To date, few observations have been reported on arm restlessness and periodic movements of the upper limbs.1,2 This variant shares common features with restless legs syndrome and periodic limb movement disorder, such as therapeutic response to dopaminergic agonists. Clinicians should be aware of restlessness of the upper limbs, which likely remains underdiagnosed and requires appropriate therapeutic management.

The onset of restless legs syndrome (RLS) is usually progressive and the neural substrates underlying its pathophysiology remain to be identifi ed. Here we report on a patient presenting with acute-onset RLS that was symptomatic of a right anteromedial pontine infarction. This case is exceptional because RLS appeared several hours before the occurrence of a regressive dysarthria clumsy-hand syndrome. Additionally, millimetric MRI sections showed that the structures possibly involved in RLS pathogenesis were the corticospinal tract, the pontine nuclei, and the pontocerebellar fi bers. Although this is uncommon, clinicians should be aware that RLS characterized by a sudden onset can be a clinical manifestation related to stroke. Keywords: pontine stroke, pontine anteromedial infarction, restless legs syndrome, RLS, periodic limb movements, RLS C A S E R E P O R T SR estless legs syndrome (RLS) is a common neurological disorder whose symptoms develop progressively.1 The neural substrates underlying RLS pathophysiology remain to be identifi ed.1 Here, we report an exceptional case of a patient who presented with acute onset RLS as the fi rst clinical manifestation of a right anteromedial pontine infarction. Additionally, we analyzed, using millimetric MRI sections, the structures affected by the lesion. REPORT OF CASEA 64-year-old patient presented a severe RLS characterized by sudden onset. He complained, for the fi rst time ever, of an urge to move the legs with paresthesia, worsened during rest and as he lay down. The symptoms were relieved by mobilization, fulfi lled the criteria of the International study group for diagnosis of RLS, and caused unusual and severe sleep-onset insomnia. The following morning the patient presented additionally with dysarthria-clumsy hand syndrome. He was a former smoker and was previously diagnosed with hypertension. Upon admission, MRI scans revealed a recent right anteromedial pontine infarction.Investigations were otherwise unremarkable, and the stroke was presumed to be atherothrombotic. Treatment consisted of aspirin, atorvastatin and nebivolol. Ten days after RLS onset, the neurological examination was normal, yet RLS persisted and was evaluated as severe (24/ DISCUSSIONWe describe the case of a patient presenting with RLS and presumably PLMS whose onset was coincident with a classic lacunar stroke syndrome (i.e., clumsy-hand dysarthria syndrome). The neural substrate and the generator(s) responsible for RLS and PLMS remain unknown. Stroke-related RLS might emerge from interrupted fi bers of presumably descending "inhibitory" pathways causing a supraspinal disinhibition. How can lesions of the paramedian pons be responsible for RLS occurrence? Using MRI with millimetric sections, we analyzed, in reference to the Duvernoy brain atlas, the structures that might be involved. Firstly, the reticular formation located in the tegmentum was spared, in contrast to previously reported