Hipólito Nzwalo

Delayed diagnosis in ALS: the problem continues.

We studied the limitations to early diagnosis in amyotrophic lateral sclerosis (ALS). The diagnostic process was assessed in 120 consecutive patients, including onset, interval to diagnosis, investigations, specialist assessment and pre-diagnostic management. Times from onset to first consultation (T1), second consultation (T2) and diagnosis (TD) were considered. Predictors of diagnostic delay were determined by multivariate logistic regression, adjusted for gender, age, clinical manifestations, and specialism of the first and second consultants. There were 101 consecutive ALS patients with complete datasets (69% men; median age at diagnosis 61.5 years). The mean TD and median TD were respectively 10.1 and 9.5 months. In 55%, the first consultant was a general practitioner (GP), in 16% a neurologist and in 14% an orthopedist. The diagnosis of ALS was made by non-neurologists in 9 patients. The odds of delayed diagnosis (≥ 12 months) were higher (1.56; 0.19-12.56) in younger patients (≤ 45 years) (p<0.05). Female gender (0.56; 0.29-1.70) and bulbar-onset (0.56; 0.29-1.70) were independently associated with earlier diagnosis (p<0.05). Assessment by a neurologist at the first (0.32; 0.19-2.46) or second consultation (0.87; 0.21-1.21) was associated with a shorter diagnosis time (< 12 months) (p<0.05). We conclude that diagnostic delay mainly resulted from delayed referral from non-neurologist physicians to a neurologist. Moreover, incomplete neurophysiological investigation had a relevant impact.

Shifting the CARASIL Paradigm Report of a Non-Asian Family and Literature Review

Background and Purpose— Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a rare form of nonhypertensive cerebral small-vessel disease caused by mutations in the HTRA1 gene. CARASIL is characterized by early adulthood onset of subcortical infarcts, cognitive impairment, alopecia, and spondylosis. Until recently, this disorder was almost exclusively reported in the Asian population. Methods— Description of the clinical, imaging, and genetic study of 2 siblings with CARASIL, with a brief comparative review of published non-Asian cases of the disease. Results— Both patients exhibited the typical phenotype: cerebral small-vessel disease, spondylosis, and abnormal hair lost. Mutation screening was performed for NOTCH3 and HTRA1 genes. No mutations were found in NOTCH3. The study revealed the presence of a homozygous c.496C>T substitution in HTRA1 in both siblings. Conclusion— This report highlights the need of considering this entity in the differential diagnosis of cerebral small-vessel disease in young patients, even in the non-Asian populations.

Late Cerebrovascular Complications After Radiotherapy for Childhood Primary Central Nervous System Tumors.

BACKGROUND Brain radiotherapy plays a central role in the treatment of certain types of childhood primary central nervous system tumors. However, damage to surrounding normal brain tissue causes different acute and chronic medical and neurological complications. Despite the expected increase in number of childhood primary central nervous system tumor survivors, studies assessing the occurrence of late cerebrovascular complications, such as cavernoma, moyamoya, microbleeds, superficial siderosis, and stroke are sparse. METHODS We undertook a retrospective consecutive case series review describing the occurrence and characteristics of late cerebrovascular complications in 100 survivors of childhood primary central nervous system tumors treated with radiotherapy. Demographic, clinical, and radiological findings including gradient echo brain magnetic resonance data were retrieved. RESULTS Late cerebrovascular complications were found in 36 (36%) of the patients included in the study. Mean age at radiotherapy was 8.6 years (3-17) and at diagnosis was 23.9 years (3-38). The majority were males (21; 58%). The most common complications were microbleeds (29/36; 80.6%) and cavernomas 19 (52.8%). In seven (19.4%), late cerebrovascular complications were symptomatic: epilepsy (two), motor and language deficit (two), and sensorineural hearing loss and progressive ataxia (three) associated with cavernomas, stroke, and superficial siderosis, respectively. Follow-up length was associated with an increased diagnosis of late cerebrovascular complications (P < 0.0001). Late cerebrovascular complications occurred more commonly in children treated with whole-brain radiation therapy (P = 0.046). Factors such as sex, chemotherapy, and histological type of tumor were not correlated with the occurrence of late cerebrovascular complications. CONCLUSION Although not usually symptomatic, late cerebrovascular complications occur frequently in survivors of childhood primary central nervous system tumors treated with radiotherapy. Prolonged follow-up increases the probability of diagnosis. The impact and prognostic value of these late cerebrovascular complications is yet to be clarified.

Sleep-related eating disorder secondary to zolpidem

Sleep-related eating disorder (SRED) is characterised by eating episodes during the first period of the night sleep with partial loss consciousness, and amnesia. It can rarely be induced by some drugs, including zolpidem. We present a video report of a patient with a 1-year history of SRED caused by zolpidem causing important repercussions in the sleep structure and life quality. The night eating episodes ceased promptly with discontinuation of zolpidem. Upon the follow-up, the sleep structure improved and the daily consequences disappeared. As in few reported cases of zolpidem-induced SRED, our patient was suffering from the parasomnia for a long time before the diagnosis. Active exclusion of symptoms suggestive of SRED in patients under zolpidem treatment can avoid the deleterious effect of the sleep disorder.

Reversible Acute Parkinsonism and Bilateral Basal Ganglia Lesions in a Diabetic Uremic Patient

The syndrome of bilateral basal ganglia lesions in diabetic uremic patients is a rare disorder mostly reported in Asians. There are few reports of the syndrome in Caucasians. It manifests as an acute hyperkinetic or hypokinetic extrapyramidal disorder in association with uniform neuroimaging findings of bilateral symmetrical basal ganglia changes in diabetics undergoing hemodialysis. Its pathophysiology remains largely unknown. Thus, we report a typical case of the syndrome in a Caucasian patient who developed an acute and reversible akinetic rigid parkinsonism secondary to bilateral basal ganglia lesions.

Delayed hypoxic-ischemic leukoencephalopathy

A 55-year-old female was found unconscious in a ventilated room. She recovered consciousness on the way to the emergency room. Her vital signs were stable. She presented with negativism and poor communication. Physical examination, routine tests, brain CT and electroencephalogram were normal. Urine toxicology was positive for benzodiazepines. Twelve days after, she presented with catatonia and immobility. Additional examinations, including cerebrospinal fluid (CSF) testing and brain CT, were again normal. Risperidone was administered, and psychotherapy intensified. In the third week, the condition worsened, with intense pyramidal signs and decerebration that led to a vegetative state. Brain MRI revealed diffuse leukoencephalopathy. Extensive metabolic and CSF studies were persistently negative. Brain biopsy was compatible with chronic cerebral hypoxia/anoxia. A diagnosis of delayed hypoxic-ischemic leukoencephalopathy was made. Supportive measures were intensified. She was discharged from the hospital after 4 months in a minimally conscious state and was capable of elementary communication and recognising faces.

Acute encephalitis as initial presentation of primary HIV infection

Acute encephalitis is a life-threatening condition. A wide variety of infectious agents are implicated and in many patients no cause is found. HIV acute seroconversion illness can rarely present as acute encephalitis. Although most experts agree in starting antiretroviral treatment in severe acute HIV infection, the evidence of the benefits are still lacking. The authors report a case of severe acute encephalitis as a primary presentation of HIV infection in which introduction of highly active antiretroviral treatment resulted in clinical recovery. This case highlights the need to consider HIV infection in the differential diagnosis of treatable viral encephalitis.

24-hour rhythmicity of seizures in refractory focal epilepsy.

The occurrence of seizures in specific types of epilepsies can follow a 24-hour nonuniform or nonrandom pattern. We described the 24-hour pattern of clinical seizures in patients with focal refractory epilepsy who underwent video-electroencephalography monitoring. Only patients who were candidates for epilepsy surgery with an unequivocal seizure focus were included in the study. A total of 544 seizures from 123 consecutive patients were analyzed. Specific time of seizures were distributed along 3- or 4-hour time blocks or bins throughout the 24-hour period. The mean age of the subjects was 37.7 years, with standard deviation of 11.5 years, median of 37. The majority were females (70/56%). The majority of patients had a seizure focus located in the mesial temporal lobe (102/83%) and in the neocortical temporal lobe (13/11%). The remaining patients had a seizure focus located in the extratemporal lobe (8/6%). The most common etiology was mesial temporal sclerosis (86/69.9%). Nonuniform seizure distribution was observed in seizures arising from the temporal lobe (mesial temporal lobe and neocortical temporal lobe), with two peaks found in both 3- and 4-hour bins: 10:00-13:00/16:00-19:00 and 08:00-12:00/16:00-20:00 respectively (p=0.004). No specific 24-hour pattern was identified in seizures from extratemporal location. The 24-hour rhythmicity of seizure distribution is recognized in certain types of epilepsy, but studies on the topic are scarce. Their replication and validation is therefore needed. Our study confirms the bimodal pattern of temporal lobe epilepsy independently of the nature of the lesion. However, peak times differ between different studies, suggesting that the ambient, rhythmic exogenous factors or environmental/social zeitgebers, may modulate the 24-hour rhythmicity of seizures. Characterization of these 24-hour patterns of seizure occurrence can influence diagnosis and treatment in selected types of epilepsy, such as the case of temporal lobe epilepsy, the most common drug-resistant epilepsy.

Acute Stroke with Concomitant Acute Myocardial Infarction: Will You Thrombolyse?

Dear Sir: Concomitant occurrence of acute myocardial infarction (MI) and stroke is infrequently encountered in emergent patients. Acute MI within the previous 3 months is considered a relative contraindication for therapy with alteplase or intravenous tissue plasminogen activator (IV rtPA).1 The use of IV rtPA for stroke in patients with a recent MI is associated with an increased risk of cardiac rupture, secondary to breakdown of the existing fibrin clot within the necrotic myocardium and/or degradation of collagen2. Whether it is appropriate to perform thrombolysis in an emergent patient with concomitant ischemic stroke and MI remains a matter for debate. A 44-year-old Caucasian man with a past history of binge drinking and heavy smoking since childhood, presented to the emergency department (ED) with a history of sudden onset of focal neurologic deficits, which had stared 1 hour previously. Neurological examination revealed dysarthria, left-sided homonymous hemianopia, facial central paresis, hemiparesis, and hemineglect (National Institutes of Health Stroke Scale [NIHSS] score, 11). His general examination was unremarkable. Blood pressure was 110/70 mmHg, temperature was 36.8℃, and pulse was 61 bpm. There was no jugular venous distension. He also complained of an intermittent vague ache in the anterior thoracic region and left shoulder, which had been present for the preceding 48 hours. The patients electrocardiogram showed signs compatible with inferior MI with 2:1 atrioventricular block (Figure 1A). Cardiac troponin I level was elevated at 16.045 ng/mL (normal value, ≤0.04 ng/mL). Emergent bedside transthoracic echocardiography showed the presence of inferior wall hypokinesis with good left ventricular systolic function. Computed tomography brain scan (brain CT) showed early signs of ischemia in the territory of the right middle cerebral artery (Figure 1B). Figure 1 (A) Electrocardiogram showing sinus rhythm, with 2:1 conduction block; two p waves (blue arrows) and one QRS wave (blue circle) are shown. ST elevation is visible in leads II, III, and aVF (red arrows), with ST depression in leads I and aVL (white arrows). ... IV t-PA (0.9 mg/kg over 1 hour, total dose 80 mg) was administered 2 h after stroke onset. The patients condition improved with thrombolysis (NIHSS score, 4). Approximately 10 hours after thrombolysis, he developed persistent bradycardia (40-50 bpm) and hypotension (100-90 mmHg systolic, 40-60 mmHg diastolic), requiring treatment with volume expanders. Transthoracic echocardiography revealed expansion of the MI to the right ventricle, without cardiac tamponade or depression of systolic function. Brain CT was repeated after 24 hours and showed the presence of ischemia in the cortical territory of the right middle cerebral artery (Figure 1C). Results of the remaining investigations, including a metabolic panel (glucose levels, hemogram, blood coagulation times, ionogram, renal function, hepatic enzymes), were normal. The patient was transferred to the intensive care unit after successful resuscitation for ventricular fibrillation. He remained in the intensive care unit for 2 consecutive weeks, during which time he had several medical complications, including refractory malignant arrhythmias with a recurrent need for resuscitation. Brain CT was repeated 8 days after the stroke and showed 2 new lesions in the posterior cerebral artery territory (Figure 1D). On discharge from the ICU, he had Psychomotor slowing, left-sided hemiparesis/hemihypesthesia and mild appendicular ataxia (NIHSS score, 9). Six months after the stroke, he resumed his normal life (Rankin 2). The inclusion of MI as a relative or absolute contraindication for IV rtPA in acute stroke is not evidence-based.1,2 Although cardiac wall rupture and tamponade are very rare in patients presenting acute stroke and MI, these complications may constitute a major barrier for IV rtPA in such patients.2 Factors known to be associated with an increased risk of cardiac wall rupture and tamponade include older age, female sex, large anterior MI, longer time from symptom onset to thrombolysis, infarct size, transmural extent, and pericardial involvement.3,4 The overall frequency of these complications is approximately 1% in patients treated with thrombolysis for acute MI.3 However, in comparison to controls, with the exception of patients older than 75 years, the occurrence of and the risk of mortality from cardiac rupture is not increased after treatment of acute MI with rtPA.3,4,5 There are no evidence-based guidelines for the management of patients with concomitant acute MI and acute stroke, nor are there published clinical studies addressing the decision-making process in such cases. Depending on the clinical picture, physicians may focus on the management of either the stroke or the MI. Obviously, independent management of one thrombosed territory will delay the treatment of the other vascular bed. Although superior to thrombolysis for acute MI,6 primary percutaneous coronary intervention would delay rtPA for stroke, increasing the risk of severe neurological disability in our case. Furthermore, intravenous heparin bolus during, and dual antiplatelet therapy (aspirin plus clopidogrel) following coronary angioplasty, would potentiate the risk of hemorrhagic complications related to rtPA for stroke. Mechanical thrombectomy for acute stroke, a procedure that is not available in most hospitals including ours, could theoretically be combined with percutaneous coronary intervention. While we did not find any single report of such combined intervention, some authors believe that in the presence of acute ischemic emergent conditions affecting different territories or organs, intravenous thrombolytic therapy is a reasonable option.7 In a patient without demographic risk factors for cardiac tamponade, we decided to offer thrombolysis in a balanced attempt to treat both myocardial and brain infarction, after excluding any relevant change on bedside transthoracic echocardiography. In conclusion, given the current knowledge limitations, treatment decisions in cases of concomitant acute MI and acute ischemic stroke should be individualized. The delicate balance between the presence or absence of risk factors for cardiac tamponade and the potential cardiac or neurological disability may guide the clinician in such a difficult scenario. Alteplase should probably not be avoided in eligible patients with ischemic stroke and MI in the absence of the aforementioned risk factors for cardiac complications associated with intravenous thrombolysis.

A family with 2 different hereditary diseases leading to early cardiac involvement.

Abstract Autosomal dominant limb-girdle muscular dystrophy type 1B (LGMD 1B) is caused by mutations in the LMNA gene. The disorder is associated with potentially fatal cardiac arrhythmias. Brugada syndrome (BS) is an autosomal dominant channelopathy linked to mutations in the SCN5A gene. BS is also associated with increased risk of sudden cardiac death. We reported a family in which a novel gene mutation, a missense mutation (c.80C>T) in exon 1 of the LMNA gene causing autosomal dominant LGMD 1B, occurred in association with SCN5A gene mutation causing BS. After the diagnosis of BS, 4 patients received implantable cardioverter–defibrillator therapy. Eight members of the family deceased at early age before the diagnosis. We emphasized the co-occurrence of 2 different conditions predisposing to sudden cardiac death: LGMD 1B caused by a novel mutation and BS.