Annals of Indian Academy of Neurology最新文献

Abstract: Mitochondrial DNA maintenance defects (MDMD) are rare genetic disorders that typically present in infancy but can manifest later with multi-organ involvement. We describe four MDMD cases (age 19-25) with distinct clinical and genetic profiles and delayed diagnosis. Two patients with mitochondrial neurogastrointestinal encephalomyopathy (homozygous TYMP variants: c.454G>T, c.866A>C) exhibited cachexia, ptosis, neuropathy, and confluent white matter hyperintensities leukodystrophy. Two others with MPV17 (c.293C>T) presented with neuromyopathy and hepatosplenomegaly; one showed novel concentric ring lesions on magnetic resonance imaging (MRI). Despite severe white matter changes/leukodystrophy, cognition was preserved. Diagnoses were delayed due to atypical gastrointestinal or neuromuscular symptoms. This series highlights the diagnostic challenge of MDMD and underscores that it should be considered in adolescents or young adults with unexplained neuropathy, white matter hyperintensities/leukodystrophy, or cachexia, even without classic hepatic or encephalopathic features. Genetic testing is essential for diagnosis, as phenotypic variability often obscures underlying MDMD. Our findings underscore the need for increased awareness of this delayed-diagnosis presentation to enable timely intervention.

Background and objectives: Early post-stroke delirium (PSD) is difficult to diagnose and complicates recovery. We aimed to evaluate two validated delirium screening tools, focusing on patients with stroke-related higher-order cognitive deficits (HOCDs).

Methods: We prospectively analyzed the delirium features and compared the diagnostic accuracy of the Confusion Assessment Method for ICU (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) with Diagnostic and Statistical Manual -5 (DSM-5) criteria in 164 patients with acute ischemic stroke. Early PSD was defined as delirium occurring within 72 h of admission.

Results: Early PSD occurred in 32.3% patients, two-thirds of whom had HOCDs such as aphasia or neglect. Individual delirium features were frequent in nondelirious patients with HOCDs, inattention (Area under curve [AUC] .98, odds ratio [OR] 28.88), psychomotor changes (AUC.95, OR 10.60), and impaired arousal (AUC.95, OR 8.57) had maximum discriminating value on logistic regression analysis. When compared with DSM-5, CAM-ICU (sensitivity 81%, specificity 84%, AUC.97) had better accuracy than ICDSC (sensitivity 70%, specificity 86%, AUC.96); however, both were noninferior. In patients with HOCDs, both had markedly reduced specificities. Adding psychomotor changes to patients who were CAM-ICU positive (CAM-ICU Plus) improved its specificity. CAM-ICU Plus (sensitivity 79%, specificity 92%, AUC.98) had the best accuracy among all the tools.

Conclusions: Early PSD is common after ischemic stroke. Available screening tools have lower specificity in patients with post-stroke cognitive deficits. CAM-ICU performed better than ICDSC. CAM ICU Plus improves the specificity of CAM ICU, which needs to be confirmed by further multicenter studies. Stroke-specific delirium screening tools are required for improving outcomes.

Background and objectives: Spinocerebellar ataxia type 2 (SCA2) is caused by cytosine-adenine-guanine (CAG) nucleotide repeat expansion in the ATXN2 gene. Mitochondrial DNA (mtDNA) haplogroups may have an influence on the disease presentation of SCA2.

Methods: A total of 217 SCA2 patients were subjected to D-loop region sequencing for inferring mitochondrial haplogroups (mt-haplogroups). The association of age of onset (AO) and mt-haplogroup was assessed using the analysis of covariance (ANCOVA) method.

Results: The major haplogroups found in SCA2 patients were H (24.9%), L (6.5%), U (17.1%), W (1.8%), M (24.9%), G (0.5%), A (2.3%), N (6.0%), J (0.9%), I (1.4%), T (2.8%), R (3.2%), D (0.9%), C (0.5%), K (0.9%), P (3.2%), and S (2.3%). AO was significantly different at the same expanded CAG repeats in SCA2 patients, showing the role of other genetic factors in the AO modifiers. The ANCOVA model revealed a significant effect of mtDNA haplogroup on AO ( P = 0.005), with variations in haplogroups adjusted for CAG repeat length. Post-hoc analyses further confirmed that haplogroup T ( P = 0.004) and haplogroup M ( P = 0.01) were significantly associated with AO compared to other haplogroups. Specifically, haplogroup M was linked to an early AO, while haplogroup T was associated with a late AO.

Conclusions: The study suggests an association between mt-halogroups and AO in SCA2, independent of CAG repeat length, with haplogroups T and M emerging as potential modifiers that may modulate disease progression. Further research is needed to explore the mechanisms behind these associations and validate the findings in larger cohorts.