E.L., a modern-day Phineas Gage: Revisiting frontal lobe injury.

Background: How the prefrontal cortex (PFC) recovers its functionality following lesions remains a conundrum. Recent work has uncovered the importance of transient low-frequency oscillatory activity (LFO; < 4 Hz) for the recovery of an injured brain. We aimed to determine whether persistent cortical oscillatory dynamics contribute to brain capability to support 'normal life' following injury. Methods: In this 9-year prospective longitudinal study (08/2012-2021), we collected data from the patient E.L., a modern-day Phineas Gage, who suffered from lesions, impacting 11% of his total brain mass, to his right PFC and supplementary motor area after his skull was transfixed by an iron rod. A systematic evaluation of clinical, electrophysiologic, brain imaging, neuropsychological and behavioural testing were used to clarify the clinical significance of relationship between LFO discharge and executive dysfunctions and compare E.L.´s disorders to that attributed to Gage (1848), a landmark in the history of neurology and neuroscience. Findings: Selective recruitment of the non-injured left hemisphere during execution of unimanual right-hand movements resulted in the emergence of robust LFO, an EEG-detected marker for disconnection of brain areas, in the damaged right hemisphere. In contrast, recruitment of the damaged right hemisphere during contralateral hand movement, resulted in the co-activation of the left hemisphere and decreased right hemisphere LFO to levels of controls enabling performance, suggesting a target for neuromodulation. Similarly, transcranial magnetic stimulation (TMS), used to create a temporary virtual-lesion over E.L.'s healthy hemisphere, disrupted the modulation of contralateral LFO, disturbing behaviour and impairing executive function tasks. In contrast to Gage, reasoning, planning, working memory, social, sexual and family behaviours eluded clinical inspection by decreasing LFO in the delta frequency range during motor and executive functioning. Interpretation: Our study suggests that modulation of LFO dynamics is an important mechanism by which PFC accommodates neurological injuries, supporting the reports of Gage´s recovery, and represents an attractive target for therapeutic interventions. Funding: Fundação de Amparo Pesquisa Rio de Janeiro (FAPERJ), Universidade Federal do Rio de Janeiro (intramural), and Fiocruz/Ministery of Health (INOVA Fiocruz).

Neurodegeneration with brain iron accumulation: A case report / Neurodegeneração com acúmulo cerebral de ferro: relato de caso

ABSTRACT Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder caused by mutation in the PANK2 gene. It is characterized by abnormal brain iron accumulation, mainly in the globus pallidus. PKAN is included in a group of disorders known as neurodegeneration with brain iron accumulation (NBIA). We report a case of atypical PKAN with its most characteristic presentation, exhibiting marked psychiatric symptoms, speech disorder and focal dystonia. Brain MRI has great diagnostic importance in this group of disorders and, in this case, disclosed the eye-of-the-tiger sign. Genetic testing confirmed the diagnosis.

RESUMO Neurodegeneração associada à pantotenato-quinase (PKAN) é uma entidade autossômica recessiva causada pela mutação do gene PANK2. Caracteriza-se por depósito cerebral anormal de ferro, particularmente nos globos pálidos. PKAN faz parte de um grupo de desordens conhecidas como neurodegeneração com acúmulo cerebral de ferro (NBIA). Relatamos um caso de PKAN atípica com sua apresentação mais característica, sendo evidentes sintomas psiquiátricos marcados, distúrbio da fala e distonia focal. A ressonância magnética de crânio possui grande importância diagnóstica neste grupo de desordens, e neste caso, demonstrou o sinal do olho de tigre. O teste genético confirmou o diagnóstico.

Neurodegeneration with brain iron accumulation: A case report.

Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder caused by mutation in the PANK2 gene. It is characterized by abnormal brain iron accumulation, mainly in the globus pallidus. PKAN is included in a group of disorders known as neurodegeneration with brain iron accumulation (NBIA). We report a case of atypical PKAN with its most characteristic presentation, exhibiting marked psychiatric symptoms, speech disorder and focal dystonia. Brain MRI has great diagnostic importance in this group of disorders and, in this case, disclosed the eye-of-the-tiger sign. Genetic testing confirmed the diagnosis.

Neurodegeneração associada à pantotenato-quinase (PKAN) é uma entidade autossômica recessiva causada pela mutação do gene PANK2. Caracteriza-se por depósito cerebral anormal de ferro, particularmente nos globos pálidos. PKAN faz parte de um grupo de desordens conhecidas como neurodegeneração com acúmulo cerebral de ferro (NBIA). Relatamos um caso de PKAN atípica com sua apresentação mais característica, sendo evidentes sintomas psiquiátricos marcados, distúrbio da fala e distonia focal. A ressonância magnética de crânio possui grande importância diagnóstica neste grupo de desordens, e neste caso, demonstrou o sinal do olho de tigre. O teste genético confirmou o diagnóstico.

Electroencephalographic frontal asymmetry and depressive symptoms in the elderly.

Although neurophysiological changes of aging are well known, there is still much to learn about cortical asymmetry in older depressed subjects. This study aimed at assessing differences between depressed and normal elderly subjects on alpha asymmetry, and to observe the correlations of this measure with depressive symptoms and quality of life. Thirty-six subjects (14 normal and 22 depressed) were assessed by EEG, depression rating scales, and SF-36. Despite the fact that compared to healthy elderly, depressive elderly subjects showed relatively greater right frontal activity (F4F3) and relatively greater left parietal activity (P4P3); this difference was not significant. The relationship between depression and frontal asymmetry was better observed in healthy elderly, where relatively greater left frontal activity was associated with less depressive symptoms.

Frontal functions in depressed and nondepressed Parkinson's disease patients: impact of severity stages.

Severity of Parkinson's disease (PD) and frontal impairment are positively correlated. Testing frontal functions in depressed/nondepressed PD patients with different severity stages may reveal whether depression leads to this impairment. We aimed to relate severity of PD to frontal functional impairment and to test if negative stimuli/depressive symptoms interfered with frontal tasks. The Stroop test and the Emotional Stroop test were performed by 46 PD patients, 18 of whom were depressed. The Hoehn and Yahr scale assessed severity of the disease. We calculated the difference in seconds for each Stroop card and the interference index (C/D) between depressed and nondepressed patients sharing the same severity of disease. The differences among the groups (depressed and nondepressed) according to the severity of the disease (mild and moderate) were compared using the Mann-Whitney test. The depressed patients had a poorer performance on the test than the nondepressed PD patients, although the difference was not statistically significant. In conclusion, there is a clinically relevant but not statistically significant difference on the performance of frontal tasks between depressed and nondepressed PD patients. Neither depression nor the severity of the disease were determinant to the poorer performance on the Stroop and the Emotional Stroop tests.

Recognizing depression in patients with Parkinson's disease: accuracy and specificity of two depression rating scale.

This study aimed to find cut-off scores for the Montgomery-Asberg rating scale (MADRS) and the Beck depression inventory (BDI) that can relate to specific clinical diagnoses of depression in Parkinson s disease (PD). Mild and moderate PD patients (n=46) were evaluated for depression according to the DSM IV criteria. All patients were assessed with the MADRS and the BDI. A "receiver operating characteristics" (ROC) curve was obtained and the sensibility, specificity, positive and the negative predictive values were calculated for different cut-off scores of the MADRS and the BDI. The Kappa statistic was calculated for different cut-off scores to assess the agreement between the clinical judgment and both scales. Depression was present in 18 patients. MADRS cut-off scores of 6 and 10 showed Kappa 0.5 and 0.56, respectively. Specificity of cut-off score of 6 was 78.6% and of cut-off score of 10 was 96.4%. Kappa agreement of BDI cut-off scores of 10 and 18 were 0.36 and 0.62, respectively. Specificity was 60.7% for 10 and 92.9% for 18. Both rating scales show similar accuracy within the ROC curves (84.3% for MADRS and 79.7% for BDI). The MADRS and the BDI show a good accuracy and correlation to the clinical diagnosis when a cut-off score of 10 is used to MADRS and a cut-off score of 18 is used to BDI to recognize depression in mild to moderate PD patients. This may help clinicians to recognize depression in PD.

Recognizing depression in patients with Parkinson's disease: accuracy and specificity of two depression rating scale

Este estudo objetivou encontrar pontos de corte da escala de depressão de Montgomery-Asberg (MADRS) e inventário de depressão de Beck (IDB) que possam estar relacionados ao diagnóstico clínico específico de depressão na doença de Parkinson (DP). Os pacientes com DP leve e moderada (n= 46) foram avaliados para depressão de acordo com os critérios diagnósticos da DSM-IV. MADRS e IDB foram aplicadas em todos os pacientes. Uma curva "receiver operating characteristics" (ROC) foi obtida calculando-se sensibilidade, especificidade, valores preditivos positivo e negativo para diferentes pontos de corte da MADRS e IDB. O índice Kappa foi calculado verificando-se a concordância entre o julgamento clínico e, ambas as escalas em diferentes pontos de corte. A depressão estava presente em 18 pacientes. Os pontos de corte 6 e 10 da MADRS evidenciaram índice Kappa de 0,5 e 0, 56 respectivamente. A especificidade para o ponto de corte 6 foi 78.6% e para o ponto de corte 10 foi 96,4%. O índice Kappa para os pontos de corte 10 e 18 do IDB foi 0,36 e 0,62 respectivamente. A especificidade foi 60, 7% para o ponto de corte 10 e 92,9% para o 18. Ambas as escalas mostraram acurácia semelhante pelas curvas ROC (84,3% para MADRS e 79,7% para IDB). A MADRS e o IDB mostraram uma boa acurácia e correlação com o diagnóstico clínico quando o ponto de corte 10 foi utilizado para MADRS e o 18 para o IDB. A sugestão de tais pontos de corte tem por objetivo auxiliar aos clínicos no reconhecimento de depressão na DP leve e moderada.

Functional and motor response to low dose olanzapine in Huntington's disease: case report.

Previous reports on the use of olanzapine in Huntington's disease (HD) used doses ranging from 10-30 mg. We report a case of HD with marked delusions and behavioral impairment assessed by the Unified Huntington's Disease Rating Scale at baseline and four months later treated with a low dose of olanzapine. The patient improved in motor, psychiatric and activity of daily living symptoms after four months of treatment. The response to a low dose of olanzapine in HD may be an indicator of efficacy in similar cases. Further randomized controlled trials can properly assess these findings.

Functional and motor response to low dose olanzapine in huntington's disease: case report

Relatos de casos sobre o uso de olanzapina na doença de Huntington (DH) usaram doses variando de 10-30 mg. Este é um relato de caso de DH avaliado pela Unified Huntington Rating Scale no início e quatro meses depois com uma dose baixa de olanzapina. A paciente melhorou dos sintomas motores, psiquiátricos e nas atividades de vida diária após os quatro meses de tratamento. A resposta a baixas doses de olanzapina na DH pode ser um indicador de eficácia em casos similares. Mais estudos controlados randomizados podem avaliar apropriadamente esses achados.