Further description of the phenotypic spectrum of neuronal ceroid lipofuscinosis type 11.

PURPOSE: Ceroid lipofuscinosis type 11 (CLN11) is a very rare disease, being reported in only 13 unrelated families so far. Further reports are necessary to comprehend the clinical phenotype of this condition. This article aims to report nine additional cases of CLN11 from nine unrelated Latin American families presenting with relatively slow disease progression. METHODS: This was a retrospective observational study including patients with CLN11. Patients were identified through an active search for GRN pathogenic variants across the entire database of next-generation sequencing (NGS) of a commercial laboratory and by contacting attending physicians to check for clinical and radiologic findings compatible with a neuronal ceroid lipofuscinosis phenotype. RESULTS: Nine CLN11 patients from unrelated families were evaluated. Age of onset varied between 3 to 17 years. The most common findings were visual impairment, cerebellar ataxia, seizures, myoclonus and cognitive decline. One patient had a previously unreported finding of cervical, perioral and tongue myoclonus. Most of the patients were able to walk unassisted after an average of 14.2 years (SD 4.76y) from disease onset. CONCLUSION: We describe nine new cases of a very rare type of neuronal ceroid lipofuscinosis (CLN11) from Latin America with a recurrent p.(Gln257ProfsTer27) and a novel p.(Cys83Ter) nonsense variant. Our findings suggest that a slowly progressive NCL might be a clue for the diagnosis of CLN11.

Secondary stabbing headache associated with intracranial tumors, aneurysms, and arteriovenous malformation: An alarming warning sign.

BACKGROUND: Stabbing headache (SH) is considered as a pure primary headache, but according to a few clinical observations it could also be secondary. Over the past decades, we have been observing the complaint of SH in patients with intracranial vascular and neoplastic lesions. OBJECTIVE: To describe a series of patients with intracranial lesions who experienced SH. METHODS: This is a cross-sectional, retrospective study of 34 patients with intracranial lesions associated with SH, admitted at Hospital das Clínicas, Federal University of Pernambuco, Brazil. RESULTS: In this series of 34 patients [29 women, 44 ± 12 years (mean ± SD)] with secondary SH, the causes were intracranial neoplasms (n = 31), cerebral aneurysms (n = 2), or arteriovenous malformation (n = 1). Pituitary tumor (n = 18), meningioma (n = 6), and vestibular schwannomas (n = 4) were the most prevalent types of intracranial neoplasms. All these lesions had intimate contact with the dura mater, including an oligodendroglioma, the only intra-axial tumor in the series. A characteristic in the secondary SH is the crescendo pattern (12/34, 35%), progressing from infrequent attacks to recurrent crises occurring several times a day. The SH lasted from 5 days to 60 months (15 ± 18 months, mean ± SD) until the correct diagnosis [16/34 (47%) of the patients ≤6 months]. The SH was triggered by the movement of the head (5/34, 15%) or Valsalva maneuver (1/34). After surgery, suppression of the SH was observed. In a few of the patients to whom dexamethasone was prescribed, the SH subsided within a few days. CONCLUSION: This study was able to identify clinical red flags associated with intracranial lesions and secondary SH, for example, recent onset of SH, exclusively unilateral (ipsilateral) at the same location, crescendo pattern, triggered by head movements, or Valsalva maneuver.

Factors Associated With In-Hospital Mortality in Very Elderly Patients With Ischemic Stroke: A Cohort Study.

INTRODUCTION: The highest mortality rates associated with ischemic stroke occur in patients of advanced age. However, studies of factors that establish the increase in hospital mortality are scanty in this population. MATERIAL AND METHODS: Epidemiologic, clinical and laboratory data, etiology and ischemic stroke subtype and complications during hospitalization were analyzed in 195 patients aged 80 years or older. In attempt to associate prognostic factor with the in-hospital mortality during first 28 days from admission, the death and survivor groups were compared. RESULTS: Among the 195 patients evaluated, the age was 85.3 ± 4.6 years with a mortality of 26.1%. Following the multivariate model, the factors associated with in-hospital mortality were: age (OR = 1.07, 95% CI = 1.00-1.20), the score less than or equal to 8 on Glasgow coma scale (OR = 22.87, 95% CI = 3.55-148.76), diabetes mellitus (OR = 3.40, 95% CI = 1.30-8.87), total anterior clinical subtype (OR = 5.15, 95% CI = 1.82-14.52) and infectious complications (OR = 8.38, 95% CI = 3.28-21.43). CONCLUSIONS: The following risk factors were associated with a higher in-hospital mortality rate in patients over 79 years of age with ischemic stroke: older age, Glasgow coma score less than or equal to 8, total anterior circulation infarction, infection, and diabetes mellitus.

Magnetic resonance imaging study cannot individually distinguish individuals with mild cognitive impairment, mild Alzheimer's disease, and normal aging.

OBJECTIVE: To evaluate the volumetric and spectroscopy aspects of hippocampus in patients with mild Alzheimer's disease (AD) and mild cognitive impairment (MCI). METHODS: A series of patients older than 65 years and with memory deficit were studied. RESULTS: The evocation of words test presented a significant reduction in the number of words recalled by the patients with MCI and mild AD as compared with the control group. Bilateral reduction of the hippocampus volume in the AD group was observed when compared to the control group. There were no statistical differences in the values of NAA/Cr, mI/Cr, Cho/Cr and mI/NAA between the groups. CONCLUSIONS: Magnetic resonance imaging study failed to individually distinguish patients with MCI, mild AD and normal aging. However, patients with mild AD presented loss of asymmetry between the right and left hippocampus, and a reduction in hippocampus volume.

Magnetic resonance imaging study cannot individually distinguish individuals with mild cognitive impairment, mild Alzheimer's disease, and normal aging / Estudo por ressonância magnética não pode diferenciar individualmente os indivíduos com declínio cognitivo leve, doença de Alzheimer leve e envelhecimento normal

Objective: To evaluate the volumetric and spectroscopy aspects of hippocampus in patients with mild Alzheimer's disease (AD) and mild cognitive impairment (MCI). Methods: A series of patients older than 65 years and with memory deficit were studied. Results: The evocation of words test presented a significant reduction in the number of words recalled by the patients with MCI and mild AD as compared with the control group. Bilateral reduction of the hippocampus volume in the AD group was observed when compared to the control group. There were no statistical differences in the values of NAA/Cr, mI/Cr, Cho/Cr and mI/NAA between the groups. Conclusions: Magnetic resonance imaging study failed to individually distinguish patients with MCI, mild AD and normal aging. However, patients with mild AD presented loss of asymmetry between the right and left hippocampus, and a reduction in hippocampus volume. .

Objetivo: Avaliar volume e espectroscopia do hipocampo em pacientes com doença de Alzheimer leve e declínio cognitivo leve. Métodos: Foi estudada uma série de pacientes com 65 anos de idade ou mais, com déficit de memória. Resultados: O teste de evocação de palavras mostrou redução significativa no número de palavras lembradas pelos pacientes com declínio cognitivo leve e doença de Alzheimer leve, em comparação com o grupo controle. Foi observada redução bilateral do volume do hipocampo no grupo com doença de Alzheimer quando comparado com o grupo controle. Não houve diferença estatística nos valores de NAA/Cr, mI/Cr, Cho/Cr e mI/NAA entre os grupos. Conclusão: Estudo pela ressonância magnética não diferencia individualmente os pacientes com declínio cognitivo leve, doença de Alzheimer leve e envelhecimento normal. No entanto, pacientes com quadro leve de doença de Alzheimer apresentam perda de assimetria entre os hipocampos direito e esquerdo e redução no volume do hipocampo. .

Mesial temporal lobe epilepsy: clinical and neuropathologic findings of familial and sporadic forms.

PURPOSE: To evaluate the clinical and hippocampal histological features of patients with mesial temporal lobe epilepsy (MTLE) in both familial (FMTLE) and sporadic (SMTLE) forms. METHODS: Patients with FMTLE (n = 20) and SMTLE (n = 39) who underwent surgical treatment for refractory seizures were studied at the University of São Paulo School of Medicine at Ribeirão Preto. FMTLE was defined when at least two individuals in a family had clinical diagnosis of MTLE. Hippocampi from all patients were processed for Nissl/HE and Timm's stainings. Both groups were compared for clinical variables, hippocampal cell densities, and intensity of supragranular mossy fiber staining. RESULTS: There were no significant differences between FMTLE and SMTLE groups in the following: age at the surgery, age of first usual epileptic seizure, history of initial precipitating injury (IPI), age of IPI, latent period, ictal and interictal video-EEG patterns, presence of hippocampal atrophy and signal changes at MRI, and postoperative outcome. In addition, no differences were found in cell densities in hippocampal cornu ammonis subfields (CA1, CA2, CA3, CA4), fascia dentata, polymorphic region, subiculum, prosubiculum, and presubiculum. However, patients with SMTLE had greater intensity of mossy fiber Timm's staining in the fascia dentata-inner molecular layer (p< 0.05). DISCUSSION: Patients with intractable FMTLE present a clinical profile and most histological findings comparable to patients with SMTLE. Interestingly, mossy fiber sprouting was less pronounced in patients with FMTLE, suggesting that, when compared to SMTLE, patients with FMTLE respond differently to plastic changes plausibly induced by cell loss, neuronal deafferentation, or epileptic seizures.

Cluster headache attacks in a woman previously struck by lightning: pathophysiology of the latent period.

BACKGROUND: Cases of patients who developed cluster headache-like symptoms after different putative causes have been reported, indicating a direct relationship between brain lesion and this particular type of headache. Long term, delayed, neurological sequelae after lightning have also been described. CASE REPORT: We describe the case of a woman who, at the age of 10, was struck by lightning. Six years later she developed cluster headache-like attacks. CONCLUSION: We hypothesize that a relationship between the lightning and the cluster headache-like episodes observed in our patient. This case study may have helped throw some light into the still unknown pathophysiology of this particular type of primary headache.

Cluster headache attacks in a woman previously struck by lightning: pathophysiology of the latent period

BACKGROUND: Cases of patients who developed cluster headache-like symptoms after different putative causes have been reported, indicating a direct relationship between brain lesion and this particular type of headache. Long term, delayed, neurological sequelae after lightning have also been described. CASE REPORT: We describe the case of a woman who, at the age of 10, was struck by lightning. Six years later she developed cluster headache-like attacks. CONCLUSION: We hypothesize that a relationship between the lightning and the cluster headache-like episodes observed in our patient. This case study may have helped throw some light into the still unknown pathophysiology of this particular type of primary headache.

INTRODUÇÃO: Foram descritos casos de pacientes que desenvolveram cefaléia em salvas como manifestação secundária à diferentes causas, indicando uma relação direta entre uma lesão cerebral e este tipo particular de cefaléia. Seqüelas neurológicas tardias após injúria elétrica por raio também têm sido descritas. RELATO DO CASO: Nós descrevemos o caso de uma mulher que aos 10 anos de idade foi atingida por um raio. Seis anos mais tarde desenvolveu sintomatologia de cefaléia em salvas. CONCLUSÃO: Acreditamos que pode haver relação entre a injúria elétrica causada pelo raio e o aparecimento dos episódios semelhantes à cefaléia em salvas observados na nossa paciente. A provável fisiopatologia envolvida na gênese da cefaléia em salvas de origem secundária é discutida, particularmente em relação ao intervalo latente entre a injúria precipitante inicial e a fase álgica da cefaléia.

Clinical and neuroimaging features of good and poor seizure control patients with mesial temporal lobe epilepsy and hippocampal atrophy.

PURPOSE: Hippocampal atrophy (HA) and signal changes, detected at magnetic resonance imaging, have been associated with intractable seizures. Such a relation has been established by tertiary centers, where the prevalence of more severe cases tends to be higher. We evaluated the clinical and imaging variables that may have relevance to seizure control in patients with mesial temporal lobe epilepsy (MTLE) and HA. METHODS: MTLE patients from the outpatient clinic of University of São Paulo School of Medicine at Ribeirão Preto were evaluated with protocols for the temporal lobe. Patients were considered to have good seizure control (GC; n = 42) if they had three of fewer seizures per year. Patients with pharmacoresistance and who did not fit the criteria for GC were considered to have poor seizure control (PC; n = 44). We made group comparisons and correlations of clinical data and hippocampal volume (HV) with seizure frequency. RESULTS: No statistical differences were observed between the GC and PC groups in the following parameters: age at the time of study, age at the time of the initial precipitating injury (IPI) or first epileptic seizure, epilepsy duration and follow-up, and family history of epilepsy. No differences were found in HV between GC (male, 2.04 +/- 0.60 cc; female, 2.00 +/- 0.70 cc) and PC (male, 2.26 +/- 0.47 cc; female, 2.15 +/- 0.48 cc) groups. Regression analysis indicated no correlation between seizure frequency and HV (p = 0.33). CONCLUSIONS: These findings suggest that the intensity of HA does not have a direct correlation with seizure frequency in patients with MTLE with HA and that the detection of HA in MTLE patients does not mean an unequivocal indication of intractability.