Case report: Late onset type 3 hemiplegic migraine with permanent neurologic sequelae after attacks.

This case study describes a 57-year-old woman with a six-year history of recurrent episodes characterized by visual, sensory, speech disturbances, hemiparesis and severe one-sided headaches accompanied by fever and altered consciousness. Initially misdiagnosed as a stroke, the atypical disease course and MRI findings led to additional genetic testing which revealed a sodium voltage-gated channel gene mutation (T1174S), confirming a diagnosis of sporadic hemiplegic migraine. The migraine prophylaxis showed some improvement in episode frequency and severity. Despite an initial improvement, the patient underwent severe cognitive decline and developed new permanent neurological symptoms during the subsequent 7 years of follow-up.

Olfactory memory in mild cognitive impairment and Alzheimer's disease.

Introduction: Olfaction is impaired in Alzheimer's disease (AD). However, olfactory memory has rarely been examined. As the pathogenesis of AD remains largely unknown, collecting more data regarding the occurrence and progression of its symptoms would help gain more insight into the disease. Objective: To investigate olfactory memory and its relationship with verbal memory and other clinical features in patients with early-stage AD. Methods: Three groups of participants were enrolled in this study: patients with mild dementia due to AD (MD-AD, N = 30), patients with mild cognitive impairment due to AD (MCI-AD, N = 30), and cognitively normal older participants (CN, N = 30). All participants underwent cognitive evaluation (Clinical Dementia Rating scale, Mini Mental State Examination, Alzheimer's Disease Assessment Scale-Cognitive Subscale, delayed verbal recall, and verbal fluency tests) and assessment of olfactory immediate and delayed recognition memory. Results: Olfactory immediate and delayed recognition memory scores were significantly lower in the MD-AD group than in the MCI-AD and CN groups. The MCI-AD and CN groups did not differ significantly [in both cases, Kruskal-Wallis test, p < 0.05; post hoc analysis revealed significant differences between the MD-AD and MCI-AD groups and between the MD-AD and CN groups (p < 0.05), and no significant difference between the MCI-AD and CN groups (p > 0.05)]. Verbal immediate recall, delayed recall after 5 min, and delayed recall after 30 min scores were significantly worse in the MD-AD and MCI-AD groups than in the CN group. MD-AD and MCI-AD groups did not differ significantly [in all cases Kruskal-Wallis test, p < 0.05; post hoc analysis revealed significant differences between MD-AD and CN groups, and MCI-AD and CN groups (p < 0.05) and no significant difference between MD-AD and MCI-AD groups (p > 0.05)]. Duration of AD symptoms was a strong predictor of both immediate and delayed olfactory recognition memory scores. Conclusion: Olfactory memory impairment was observed in patients with AD. The changes progress during the course of the disease. However, unlike verbal memory, olfactory memory is not significantly impaired in the prodromal stage of AD.

Odor Discrimination as a Marker of Early Alzheimer's Disease.

BACKGROUND: Olfactory dysfunction is an early symptom of Alzheimer's disease (AD). However, olfactory tests are rarely performed in clinical practice because their diagnostic efficacy in detecting early AD is unclear. OBJECTIVE: To investigate odor discrimination in patients with early AD and the efficacy of olfactory discrimination tests in differentiating these patients from subjects with normal cognition (CN). METHODS: Thirty patients each with mild dementia due to AD (MD-AD) and mild cognitive impairment due to AD (MCI-AD) and 30 older subjects with CN were enrolled. All participants underwent cognitive examinations (CDR, MMSE, ADAS-Cog 13, and verbal fluency) and odor discrimination tests (Sniffin' Sticks test, Burghart®, Germany). RESULTS: The MD-AD group achieved significantly worse scores on the olfactory discrimination test than the MCI-AD group, and the MCI-AD group achieved significantly worse results than the CN group (p < 0.05). A cut-off score of≤10 had a diagnostic accuracy of 94.44% (95% CI, 87.51-98.17%) in differentiating patients with MCI-AD/MD-AD from subjects with CN and of 91.67% (95% CI, 81.61-97.24%) in differentiating those with MCI-AD from subjects with CN. Our multinomial logistic regression model with demographic data and ADAS-Cog 13 scores as predictor variables correctly classified 82.2% of the cases (CN, 93.3%; MC-AD, 70%; MD-AD, 83.3%); on adding the olfactory discrimination score to the model, the percentage increased to 92.2% (CN, 96.7%; MCI-AD, 86.7%; MD-AD, 93.3%). CONCLUSION: Odor discrimination is impaired in cases of early AD and continues to deteriorate as the disease progresses. The olfactory discrimination test showed good diagnostic efficacy in detecting early AD.

Brief Test of Olfactory Dysfunction Based on Diagnostic Features of Specific Odors in Early-Stage Alzheimer Disease.

BACKGROUND Olfactory impairment is an early symptom of Alzheimer disease (AD). However, it is rarely assessed in clinical practice. This study aimed to assess the identification and discrimination of specific odors in patients with early-stage AD using the Sniffin' Sticks test and determine the items that would be most valuable in the diagnosis of early-stage AD in order to create a brief test of olfactory dysfunction. MATERIAL AND METHODS Three groups of participants were enrolled, including 30 patients with mild cognitive impairment due to AD (MCI-AD group), 30 with mild dementia due to AD (MD-AD group), and 30 older participants with normal cognition (NC group). All participants underwent cognitive (Clinical Dementia Rating, Mini-Mental State Examination, Alzheimer's Disease Assessment Scale-Cognitive Subscale, and verbal fluency tests) and olfactory (Burghart Sniffin' Sticks odor identification and odor discrimination tests) assessments. RESULTS The MD-AD group scored significantly lower than the MCI-AD group and the MCI-AD group scored significantly lower than the NC group in both the odor identification (P<0.001) and discrimination (P<0.05) tasks. The shortened versions of the odor identification and discrimination tasks showed good diagnostic properties in differentiating patients with AD from the NC participants (receiver operating characteristic [ROC] area under the curve [AUC]=0.912 and 0.954, respectively) and differentiating patients with MCI-AD from the NC participants (ROC AUC=0.871 and 0.959, respectively). CONCLUSIONS The brief versions of olfactory tests, containing selected items that were found to differ the most between cognitively normal participants and early-stage AD patients, have good diagnostic qualities and can aid clinicians in screening for early-stage AD.

Properties of odor identification testing in screening for early-stage Alzheimer's disease.

Odor identification (OI) is impaired in the early stages of Alzheimer's disease (AD). However, data regarding the diagnostic properties of OI tests are lacking, preventing their clinical use. We aimed to explore OI and determine the accuracy of OI testing in screening for patients with early AD. In total, 30 participants with mild cognitive impairment due to AD (MCI-AD), 30 with mild dementia due to AD (MD-AD), and 30 cognitively normal elderly participants (CN) were enrolled, and cognitive examination (CDR, MMSE, ADAS-Cog 13, and verbal fluency tests) and assessment of OI (Burghart Sniffin' Sticks odor identification test) were performed. MCI-AD patients scored significantly worse in OI than CN participants, and MD-AD patients had worse OI scores than MCI-AD patients. The ratio of OI to ADAS-Cog 13 score had good diagnostic accuracy in differentiating AD patients from CN participants and in differentiating MCI-AD patients from CN participants. Substitution of ADAS-Cog 13 score with the ratio of OI to ADAS-Cog 13 score in a multinomial regression model improved the classification accuracy, especially of MCI-AD cases. Our results confirmed that OI is impaired during the prodromal stage of AD. OI testing has a good diagnostic quality and can improve the accuracy of screening for early-stage AD.

Novel In-Frame Deletion in HTRA1 Gene, Responsible for Stroke at a Young Age and Dementia-A Case Study.

Biallelic mutations in the high-temperature requirement A serine peptidase 1 (HTRA1) gene are known to cause an extremely rare cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), which belongs to the group of hereditary cerebral small vessel diseases and is mainly observed in the Japanese population. Even though this pathology is inherited in an autosomal recessive manner, recent studies have described symptomatic carriers with heterozygous HTRA1 mutations who have milder symptoms than patients with biallelic HTRA1 mutations. We present the case of a Lithuanian male patient who had a stroke at the age of 36, experienced several transient ischemic attacks, and developed an early onset, progressing dementia. These clinical symptoms were associated with extensive leukoencephalopathy, lacunar infarcts, and microbleeds based on brain magnetic resonance imaging (MRI). A novel heterozygous in-frame HTRA1 gene deletion (NM_002775.5:c.533_535del; NP_002766.1:p.(Lys178del)) was identified by next generation sequencing. The variant was consistent with the patient's phenotype, which could not be explained by alternative causes, appeared highly deleterious after in silico analysis, and was not reported in the medical literature or population databases to date.

Fatal Liver and Lung Alveolar Echinococcosis with Newly Developed Neurologic Symptoms due to the Brain Involvement.

The fox tapeworm Echinococcus multilocularis causes human alveolar echinococcosis, commonly affecting the liver. However, in ∼1% of cases, systematic spread of the disease involves the brain as well. A patient had a 6-year history of liver and lung alveolar echinococcosis that was considered not suitable for surgery, and treatment with albendazole was introduced. After the appearance of neurologic disturbances, an intracranial mass lesion was demonstrated by radiologic imaging. The lesion was surgically removed, and histologic analysis revealed metacestode tissue of E. multilocularis . Despite the surgical resection of the lesion, the patient died of progression of systemic alveolar echinococcosis. The authors highly recommend implementing neurologic monitoring to the follow-up algorithm for patients with systemically disseminated alveolar echinococcosis. When neurologic symptoms occur, radiologic imaging of the brain should be obtained immediately. Surgery should be considered for all intracranial echinococcal lesions, unless the lesion is located in the eloquent brain area.

Distinctive Effect of Donepezil Treatment on P300 and N200 Subcomponents of Auditory Event-Related Evoked Potentials in Alzheimer Disease Patients.

BACKGROUND: Latency of P300 subcomponent of event-related potentials (ERPs) increases in Alzheimer disease (AD) patients, which correlate well with cognitive impairment. Cholinesterase inhibitors (ChEIs) reduce P300 latency in AD patients with parallel improvement in cognition. It is not known whether N200 response to ChEIs is similar to that of P300. The aim of this study was to evaluate and compare characteristics of P300 and N200 in AD patients, treatment-naïve and on stable donepezil treatment, matched by age, education, sex, and cognitive function. MATERIAL AND METHODS: We recruited 22 consecutive treatment-naïve AD patients (AD-N group), 22 AD patients treated with a stable donepezil dose of 10 mg/day for at least 3 months (AD-T group), and 50 healthy controls were recruited. Neuropsychological testing (MMSE, ADAS-Cog, and additional tests) and ERP recording was performed and analyzed. RESULTS: All groups did not differ according to age, duration of education, or sex (p>0.05). AD-N and AD-T groups did not differ according to cognitive function. The AD-T group had longer duration of disease than the AD-N group (p<0.001). The AD-T and AD-N groups did not differ in P300 latencies (p=0.49). N200 latency was longer in the AD-T group (p<0.001). The general linear model showed that significant predictors of P300 latency were age (p=0.019) and AD treatment status (p<0.001). Duration of AD was a significant predictor of N200 latency (p=0.004). CONCLUSIONS: The response of N200 latency to donepezil treatment differs from the response of P300. P300 is a better marker of ChEI treatment-dependent cognitive functions. N200 is more dependent on the duration of AD.