Rogelio Simón

Spontaneous carotid and vertebral artery dissection in children

Carotid and vertebral artery dissection is a rarely reported cause of stroke in childhood and adolescence, especially if there is not a direct trauma to the neck. Four patients, under 15 years of age, presented with an internal carotid artery dissection, and one patient presented with a vertebral artery dissection. They were all making a physical effort when the event occurred. The five patients had ischemic symptoms, and in two the events were preceded by transient ischemic attacks. Headache was associated in four patients. The diagnosis was made by magnetic resonance imaging and angiography, which included transfemoral angiography in two patients. All improved before leaving the hospital, and four patients did not suffer recurrent episodes. The diagnostic accuracy of artery dissection has improved because of noninvasive neuroimaging testing, but it should still be suspected in any pediatric ischemic stroke, especially if there is headache or cervical pain associated.

Cognitive and behavioral profile in females with epilepsy with PDCH19 mutation: Two novel mutations and review of the literature

Mutation in the protocadherin 19 (PCDH19) gene is an increasingly recognized cause of epilepsy in females. This disorder is frequently associated with mental retardation and psychiatric features. We describe two unrelated females with novel PCDH19 missense mutations. One was de novo, and the other was inherited from her unaffected father. Both had mild mental impairment but had remarkable behavioral problems. We reviewed the cognitive and behavioral profiles of previously reported PCDH19-positive cases. Intellectual disability appeared in 75% of patients, ranging from borderline to severe. More than half of the individuals presented behavioral disturbances, which could be divided into two different groups: autistic and non-autistic. The majority of patients with autism already had some degree of cognitive impairment. It appears that seizures tend to diminish or even stop in adolescence, so non-epileptic problems can become the most important and disabling issue in adult patients with PCDH19 mutation.

Vertebral artery fibromuscular dysplasia: an unusual cause of stroke in a 3-year-old child

Fibromuscular dysplasia (FMD) is a systemic arteriopathy which tends to affect renal arteries followed by cervicocranial vessels. It can lead to cerebral infarction if cephalic arteries are involved. FMD is an unusual cause of stroke in childhood that generally affects the carotid area. Only four cases of vertebral FMD and subsequent stroke have been reported previously and we present the youngest patient of all. A healthy 3-year-old female was admitted to Hospital Doce de Octubre in Madrid, Spain with cerebellar infarction. Angiography disclosed basilar artery thrombosis and typical signs of FMD in both vertebral arteries. No other angiographic alteration was noted in the other vessels studied. Her phenotype and other investigations were unremarkable. The patient was treated with anti-aggregation therapy (aspirin) and the outcome was excellent. Investigation of the occurrence in childhood of this kind of arteriopathy may lead to clarification of its natural history and speculation about its unclear pathogenesis.

Levetiracetam-Induced Reversible Autistic Regression

Levetiracetam is a commonly prescribed antiepileptic drug, and is generally well tolerated, but can eventually cause behavioral disturbances. These disturbances seem more frequent in children and in patients with a previous psychiatric history. We report on reversible autistic regression induced by levetiracetam in a 6-year-old girl with spastic cerebral palsy, mild cognitive deficiency, and focal epilepsy. She was diagnosed with pervasive developmental disorder, and demonstrated mild to moderate impairment in pragmatic language and interactions with peers. After the introduction of levetiracetam, she developed stereotypies, and her social and communicative skills deteriorated severely. She also exhibited mood lability. When the medication was discontinued, a dramatic response occurred, with a complete resolution of new abnormal findings. Levetiracetam can provoke unusual behavioral adverse effects in certain patients who are biologically more vulnerable.

Syringomyelia secondary to posthemorrhagic hydrocephalus in a preterm infant.

Syringomyelia is often associated with hydrocephalus, especially in Chiari malformations, but it has never been described as a complication of posthemorrhagic hydrocephalus after preterm birth. We report on a premature infant who presented this exceptional association. He was born at 29 weeks of gestational age and suffered a grade 3 intraventricular hemorrhage. Progressive ventricular dilatation developed despite repeated lumbar punctures, and a ventricular reservoir had to be inserted for cerebrospinal fluid drainage. Two weeks later he presented a flaccid, areflexic paralysis of his left upper limb. Magnetic resonance imaging disclosed a remarkable tetraventricular hydrocephalus and a cervical hydrosyringomyelia expanding from the C(5) to T(1) segments. After shunt surgery, the cephalic perimeter stabilized, and the infant began to move his arm. On follow-up, a minimal paresis of the left hand persisted. This case highlights an unreported outcome of posthemorrhagic hydrocephalus. In this context, syringomyelia should be included in the differential diagnosis of any infant with who presents segmental signs of acute or progressive onset.

Clinical Features and Molecular Characterization of a Patient With Muscle-Eye-Brain Disease A Novel Mutation in the POMGNT1 Gene

Muscle-eye-brain disease is a congenital muscular dystrophy characterized by structural brain and eye defects. Here, we describe a 12-year-old boy with partial agenesis of corpus callosum, ventriculomegaly, flattened brain stem, diffuse pachygyria, blindness, profound cognitive deficiencies, and generalized muscle weakness, yet without a clear dystrophic pattern on muscle biopsy. There was no glycosylation of α-dystroglycan and the genetic screening revealed a novel truncating mutation, c.1545delC (p.Tyr516Thrfs*21), and a previously identified missense mutation, c.1469G>A (p.Cys490Tyr), in the protein O-mannose beta-1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) gene. These findings broaden the clinical spectrum of muscle-eye-brain disease to include pronounced hypotonia with severe brain and eye malformations, yet with mild histopathologic changes in the muscle specimen, despite the absence of glycosylated α-dystroglycan.

MR Spectroscopy of a Bright Cerebellar Lesion in a Patient with Langerhans Cell Histiocytosis

We have read with interest the paper by Prosch et al[1][1] published in the American Journal of Neuroradiology concerning the long-term MR imaging course of 9 patients diagnosed with Langerhans cell histiocytosis (LCH). We were particularly interested in the evolution of MR abnormalities of

Myorhythmia-Like Dyskinesia Affecting the Face and Ear Associated With Anti–N-Methyl-d-Aspartate Receptor Encephalitis

Involuntary ear movements are extremely uncommon and only a few cases have been reported. This unusual focal dyskinesia is characterized either as tic, dystonia, myoclonus, or chorea. Some cases are psychogenic, as suggested by temporally related psychological stresses, associated psychiatric symptoms, and improvement with psychological treatment. In other cases, there may be a temporal relationship with certain medications, such as paroxetine. Exceptionally, ear chorea has been described in a Huntington’s disease patient. We report on a previously healthy 14-year-old male with anti–N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis who developed involuntary left ear movements during the course of his disease. He was admitted after two generalized seizures. The EEG showed a focal slowness in the right frontal lobe without epileptic abnormalities. Brain MRI was normal, and he was discharged with valproic acid. Forty-eight hours later, he presented to the emergency room with choreoatheoid movements in his left upper limb (see Video 1). Subsequently, there was a dramatic worsening of signs with left hemichorea and left orofacial dyskinesias. There were no abnormal movements on the right side of his body. Behavior changes were observed with mental slowness and progressive inhibition. After 3 days, his level of consciousness was severely impaired and he was admitted to the intensive care unit. Nevertheless, mild choreic movements persisted. At that time, an abnormal hyperkinetic movement on the left ear was noticed. It consisted in retraction of the ear, in an irregular and unpredictable way (less than 15 times per minute; see Video 2). There was an intermittent twitching of the left nasolabial fold as well. An extensive blood and cerebrospinal fluid (CSF) workup was performed. There was a mild mononuclear pleocytosis (100 cells/mm), and CSF analysis identified anti-NMDAR antibodies. A second brain MRI was normal. No tumor was identified. Treatment with corticosteroids followed by plasmapheresis and intravenous immunoglobulins resulted in marked clinical response. Encephalopathy improved progressively. Ear dyskinesia subsided in 1 week, despite the persistence of very subtle choreic movements involving his left hand. Two months later, he achieved complete recovery, and after 2 years’ follow-up, he has had no relapses. To the best our knowledge, this is the first report of ear dyskinesia associated with anti-NMDAR encephalitis. It is a treatable condition, and it resolved with immunotherapy. Movement disorders are very common during the course of the disease, and they have been reported in 84% of children with anti-NMDAR encephalitis, even as an early feature. They consist mostly in orolinguofacial dyskinesias followed by choreoathetosis, and different abnormal movements may coexist in the same patient. The orofacial dyskinesias observed in this disorder have been described as “grimacing,” “chewing,” “facial twitching,” “tongue thrusting,” and other involuntary movements involving the face, mouth, and jaw that lack a proper terminology. The phenomenology of the hyperkinetic involuntary ear and facial movements in the present case is open to interpretation. Chorea is a random-appearing sequence of discrete movements. It is distinguished from dystonia because of the apparently unpredictable, continuously ongoing nature of the movements compared with the more stereotyped movements or fixed postures of dystonia. When chorea affects proximal joints, such as shoulder or hip, this leads to large amplitude movements of the limbs called ballism. Myoclonus is characterized by repetitive and possibly rhythmic brief asymmetric shock-like movements, whereas tremor is defined by rhythmic oscillating movements. Tics are stereotyped, predictable, and

LAMA2-related congenital muscular dystrophy complicated by West syndrome

BACKGROUND Mutations in the LAMA2 gene cause autosomal recessive laminin α2 related congenital muscular dystrophy. In patients with partial laminin α2 deficiency the phenotype is usually milder than in those with absent protein. Apart from the typical white matter abnormalities, there is an increased risk of cerebral complications such as epilepsy and mental retardation, despite a structurally normal brain. METHODS/RESULTS We present a patient with primary partial laminin α2 deficiency due to a homozygous novel LAMA2 missense mutation who developed West syndrome in his first year of life. To our knowledge, this combination has not previously been reported. A 5 year-old boy exhibited global hypotonia with generalized muscle weakness from birth. At 8 months of age he presented infantile spasms and an EEG finding of hypsarrhythmia. Seizures were controlled in a few weeks with intramuscular synthetic ACTH, followed by valproic acid. Two years later antiepileptic medication was withdrawn. He achieved unsupported walking at the age of 4, but his cognitive status corresponded to a 2 year-old child. Epilepsy has not recurred and brain MRI showed the typical white matter abnormalities without associated neuronal migration defects. CONCLUSION This report widens the clinical spectrum of cerebral manifestations related with mutations in LAMA2. The beginning of a severe epileptic encephalopathy modifies the natural history of the disease.