Jesús Calleja

Charcot-Marie-Tooth disease type 1A with 17p duplication in infancy and early childhood: a longitudinal clinical and electrophysiologic study.

Objective: We describe longitudinal clinical and electrophysiologic evaluation of Charcot-Marie-Tooth disease type 1A (CMT-1A) in infancy and early childhood. Background: The clinical picture and electrophysiologic evaluation of CMT-1A during the age of nerve conduction maturation have not been documented. Design/Methods: Twenty at-risk children from six unrelated CMT-1A families were examined in the first 5 years of life. Initial ages were 1 month to 4 years (mean, 1.5 years) and final ages 4 to 19 years (mean, 9 years). All subjects had two or more motor and sensory conduction velocities (MCV and SCV), corrected distal motor latencies (DML), and F-waves. Results: Twelve children were affected. Initially, two of these (17%) had symptoms, whereas five (42%) were symptomatic at the end. Numbers of abnormal examinations at the beginning was six (50%) and at conclusion was 10 (83%). None of the patients were disabled. From 2 years of age, all affected children had abnormal MCV, SVC, F-waves, and DML. Prolonged DML was already present in the first months of life and preceded slowing of MCV in three cases. Conclusion: The electrophysiologic studies were concordant with the presence or absence of the CMT-1A DNA duplication. In most CMT-1A patients, symptoms appear in early childhood, although the florid clinical picture does not occur until the second decade of life. Serial electrophysiologic studies can detect the CMT-1A gene carrier in infancy.

Clinico-electrophysiological correlation of extensor digitorum brevis muscle atrophy in children with Charcot–Marie–Tooth disease 1A duplication ☆

The purpose of the study is to describe the electrophysiologic abnormalities accounting for the appearance and progression of extensor digitorum brevis (EDB) muscle atrophy in Charcot-Marie-Tooth-disease type 1A (CMT-1A) children. Twelve children with CMT-1A duplication were serially evaluated. Initial ages of clinico-electrophysiological exams ranged from 1 month to 4 years (mean: 2 years) and final ages from 6 to 23 years (mean: 13). All subjects had two or more electrophysiological studies of the peroneal nerve. EDB atrophy was observed in two out of 12 (17%) patients by the age of 5, in eight out of ten (80%) examined between 5 and 9 years, and in all eight (100%) patients who had reached the second decade at the end. Nerve conduction maturation was systematically abnormal, but by age of 5 the mean values of nerve conduction parameters of peroneal nerve did not significantly differ from those in older patients. Compound muscle action potential (CMAP) amplitudes of EDB were reduced in 42% of cases initially and 100% upon last exam. Furthermore, a constant finding throughout the study was progressive attenuation of CMAPs, these becoming unobtainable in four cases. EDB muscle atrophy in CMT-1A children is an age-dependent sign which is accounted for by gradual reduction of the distal peroneal nerve CMAP amplitudes.

Brain-stem auditory evoked potentials and blink reflex in friedreich's ataxia

SummaryThe brain-stem involvement in Friedreichs ataxia (FA) was studied by using brain-stem auditory evoked potentials (BAEPs) and the blink reflex. Ten out of 18 patients had abnormal BAEPs, the main abnormality being complete absence of responses and disappearance of wave V. Combined degeneration of the peripheral and central acoustic pathways probably accounts for these findings. The blink reflex was abnormal in 50% of the cases. The outstanding abnormality was bilateral delay of late responses with normal early response, which could be correlated with the known pallor of the descending trigeminal tracts. In contrast with BAEP findings, blink reflex abnormalities did not correlate with either the age of patients or the severity and duration of the disease. These data suggest a difference in susceptibility to degeneration between the auditory system and neuronal system subserving the blink reflex. We conclude that systematic BAEP and blink reflex recording is useful in the electrophysiological evaluation of FA patients.

Guillain–Barré syndrome after rituximab in a patient with idiopathic thombocytopenic purpura: a causal association?

Guillain–Barre syndrome (GBS) is an acute demyelinating inflammatory polyradiculoneuropathy characterised by rapidly progressing predominantly motor impairment and areflexia. Studies in patients and animals have provided convincing evidence that GBS is caused by an aberrant autoimmune response that damages peripheral nerves [1]. GBS rarely develops in patients who suffer from other autoimmune conditions, such as idiopathic thrombocytopenic purpura (ITP), which suggests a shared immune response [2–11]. Rituximab is a monoclonal antibody particularly efficacious in the treatment of several haematological cancers, which has also been used for the treatment of some autoimmune conditions [12]. Here we report on a patient with ITP who developed a typical GBS after treatment with rituximab. This 86-year-old man, with the antecedents of arterial hypertension, chronic obstructive lung disease and atrial fibrillation, consulted in December, 2008, due to purpuric lesions in the lower limbs. He was diagnosed as ITP. His platelet count was 5,000/mm. He received intravenous immunoglobulins (ivIG) 1 mg/kg/day for 2 days plus a descending treatment with oral prednisone (beginning with 1 mg/kg/day) for 1 month. His platelet count after this treatment was 250,000. In January, 2009, he was admitted again because his blood sample showed 10,000 platelets. He was treated with oral prednisone 1 mg/kg/day for 16 consecutive days. This treatment was stopped due to persistent thrombocytopenia (20,000 platelets). IvIG 1 g/kg/day for 2 days and intravenous rituximab (750 mg once a week for 4 weeks) were administered. His platelet count before the last rituximab dose (27 February 2009) was 121,000. Thirty-nine days after the last dose of rituximab (8 April 2009) he developed an acutely ascending progressive tetraparesis. On admission, two days after the beginning of the clinical picture, symmetric weakness, 4/5 in the upper extremities and 3/5 in lower extremities, and universal arreflexia were found. Plantar responses were flexor. Sensory examination was normal and sphincters were not affected. Platelet count was 192,000/mm. A lumbar tap was performed on admission. Glucose levels were normal, there were no cells and protein concentration was 57 mg/dl. The remaining routine laboratory determinations, including tumor markers and a complete autoimmune profile, were normal. With the presumptive diagnosis of Guillain–Barre syndrome, treatment with ivIG 0.4 g/kg/day for 5 days was given. An electrophysiological study, performed six days after the beginning of the symptoms, disclosed slowing of motor conduction velocities (MCV) in all studied nerves. MCV were markedly delayed (\32 m/s) in peroneal and tibial nerves, and slightly slowed in median and ulnar nerves (46 and 49 m/s, respectively). Motor distal latencies (MDL) were clearly prolonged in tibial and medial nerves and within normal limits in peroneal and ulnar nerves. F waves could not be obtained in right peroneal nerve, right posterior tibial nerve and right median nerve, and were delayed in right ulnar nerve. There was attenuation of distal compound muscle R. Jaso C. Valero Services of Internal Medicine, University Hospital Marques de Valdecilla, Santander, Spain

Localisation-related nonconvulsive status epilepticus: Further evidence of permanent cerebral damage.

Sirs: Although important progress about the types and aetiologies of nonconvulsive status epilepticus (NCSE) has been reported in the recent decades, the potential risk and harmful effects of an episode of complex partial status epilepticus (CPSE), a type of localisationrelated NCSE, remain undetermined. Thus, detailed serial electrophysiologic studies accompanied by pathological correlations in humans are scarce [1, 6]. A 75-year-old man recovering from aortic surgery experienced an episode of hypotension. He was transferred to the cardiovascular intensive care unit (ICU) where propofol infusion was started. There was no previous documented history of seizures, encephalitis or head trauma. On day 10, he presented with repetitive episodes of clonic movements of the left arm evolving to hemiconvulsive seizures. At that time the dosage of propofol was diminished and the patient was awake but remained slightly confused. During a portable electroencephalogram (EEG) four motor seizures arising from the right hemisphere were recorded. Although antiepileptic therapy with intravenous phenytoin (100 mg/8h) was begun, motor seizures recurred. Treatment with intravenous phenobarbital (100 mg/ 24h) was added and sedation with propofol was replaced by thiopental anaesthesia. The patient remained sedated and seizures were completely controlled. On day 15, sedation with thiopental was stopped. The patient was conscious but markedly confused. On day 18, a second portable EEG showed frequent and recurrent seizure activity arising from the right temporo-occipital junction and spreading rapidly to the temporal areas (Fig. 1). During these episodes overt convulsive activity was absent, and localisation-related NCSE was considered as the cause of the confusional state. Propofol infusion was restarted and serial portable EEGs were carried out. During these recordings special attention was paid to the detection of epileptiform discharges and recurrent focal seizures. On day 25, NCSE was controlled. Although his hospital course was complicated by numerous medical problems, all systemic variables were carefully monitored. The patient was eventually discharged to the cardiac ward thirtythree days after his hospital admission. The clinical evolution of the patient was satisfactory and his mental status was considered normal. On day 37, the patient developed bradycardia and became hypotensive abruptly followed by cardiac arrest from which he could not be resuscitated. Permission for autopsy was obtained. Macroscopic examination revealed arteriosclerosis on the arteries of the circle of Willis predominantly in the right posterior cerebral artery. There was symmetric bilateral ventricular dilatation involving mainly the frontal horns. An area of loss of consistency was identified in the right parietal lobe. Microscopic examination showed arteriosclerosis and arteriolosclerosis with status cribosus in the basal ganglia. There was an infarct in the process of colliquative necrosis with infiltrates of macrophages (stage II of Spatz) localised in the territory of the right parieto-occipital artery. Neuronal loss and astrocytic gliosis was observed in the right Ammon’s horn more marked in the CA4 pyramidal cell layer and there was satellitosis and neuronophagia in Sommer’s sector (CA1) (Figs. 2 and 3). Accumulations of NF-positive degenerated axons (“axon retraction balls”) were also seen in CA4 on the right side. Although a slight degree of gliosis was also seen in CA4 in the left hippocampus, these changes were notably less pronounced than on the contralateral side. In addition, Tau-positive neurofibrillary degeneration associated with GFAP-positive astrocytic gliosis was observed in CA4 sector of the hippocampus, gyrus dentatus and amygdaloid nucleus in both sides. Other brain regions did not show any remarkable pathological changes. We had the rare opportunity to study the brain specimen of a patient with a detailed clinical and electroencephalographic history and whose mental status seemed to be grossly normal after a prolonged episode of localisationrelated NCSE. The remarkable pathological abnormalities seen in the right hippocampus seem to suggest that the existence of a long-lasting CPSE was associated with permanent secondary damage in the meseolimbic structures. In the past, enduring cognitive and memory deficits have been described in individuals who had experienced CPSE [2, 4, 5]. Wasterlain et al. [6] mentioned informally their experience with three patients without prior epilepsy with NCSE whose LETTER TO THE EDITORS

Castleman's disease associated with chronic inflammatory demyelinating polyradiculoneuropathy: a clinical and electrophysiological follow-up study

Castlemans disease (CD), or angiofollicular lymph node hyperplasia, is a rare lymphoproliferative disorder that can be associated with peripheral neuropathy. We report the long-term follow-up of a patient with a chronic inflammatory demyelinating polyradiculoneuropathy complicating the mediastinal form of classic CD who improved notably with immunosuppressive therapy. Our findings suggest that serial electrophysiological studies may be useful for monitoring treatment efficacy.

Friedreich's ataxia presenting with pure sensory ataxia: a long-term follow-up study of two patients

We describe two patients with Friedreichs ataxia whose presenting symptomatology was for years progressive tabetic ataxia. Based upon the initial clinical, electrophysiological and nerve biopsy data, a diagnosis of idiopathic sensory neuropathy was established. Subsequent examination of the kin showed that three sisters of case 1 had Friedreichs ataxia. Upon serial clinical and electrocardiographic study, both patients eventually developed a florid Friedreichs ataxia, including cardiomyopathy. Our findings indicate that at onset Friedreichs ataxia may be indistinguishable from sensory neuropathy and also that serial examination and investigation of kinship are essential steps for accurate diagnosis.

Charcot-Marie-Tooth disease

Charcot-Marie-Tooth disease encompasses a group of disorders called hereditary sensory and motor neuropathies that damage the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound. Damage to the peripheral nerves that worsens over time can result in alteration or loss of sensation and wasting (atrophy) of muscles in the feet, legs, and hands.

Periodic eye opening and swallowing movements associated with post-anoxic burst-suppression EEG pattern

We report a video-electroencephalogram study of a 50-year-old woman who developed a clinical picture consisting of stereotyped periodic eye opening followed by eye closing, with or without swallowing movements, after a prolonged cardiopulmonary arrest. These movements were associated with a burst-suppression pattern on the electroencephalogram. [Published with video sequences].

Stimulus-sensitive post-anoxic focal motor seizures evolving into generalised myoclonic status epilepticus: a video-EEG study

We describe the case of a 62-year-old man who developed stimulus-induced focal motor seizures after prolonged cardiac arrest. During a video-EEG study, these focal motor seizures progressed into a generalised myoclonic status epilepticus. Both the severely decremented background activity on the EEG, and the absence of median and trigeminal somatosensory evoked potentials were in keeping with a devastating post-hypoxic encephalopathy and the patient died. Our clinical and electrophysiology data suggest that generalised myoclonic status epilepticus may occur in patients in whom the existence of severe cerebral damage prevents a complete development of all phases of classic generalised tonic-clonic seizures.