Association of severe hyposmia and frontal lobe dysfunction in patients with Parkinson's disease.

BACKGROUNDS AND OBJECTIVES: Severe hyposmia (SH) is a prodromal symptom of dementia associated with Parkinson's disease (PD) caused by Lewy bodies deposited in the limbic regions that connect the frontal and temporal lobes. We aimed to clarify the association between hyposmia and frontal lobe dysfunction (FLD) among patients with PD. METHODS: Patients with PD and Hoehn & Yahr stage 1-3 at on-periods without apparent dementia were screened. FLD was defined as a score of ≤14 on the Frontal Assessment Battery (FAB). SH was defined as an average recognition threshold >4 in the T&T Olfactometer. For each subscore, a recognition score of ≥4 was defined as SH. We examined whether SH and its subscores were associated with FLD and evaluated which FAB subscore might be lower in PD patients with SH using Poisson regression analysis with a robust variance estimator. RESULTS: We included 189 patients (median age, 68 years; 107 [57 %] male). FLD was observed in 53 (28 %) patients. Multivariable analysis showed that SH (PR 1.789, 95 % confidence intervals (CI) 1.115-2.872, p = 0.016) was associated with FLD. Regarding odor domains, only SH for fruity smells was associated with FLD (PR 1.970, 95 % CI 1.306-2.972, p = 0.001). Patients with SH had a higher subscore only for FAB-1 (similarity [conceptualization], p = 0.030), indicating linguistically mediated executive dysfunction. CONCLUSION: In patients with PD, SH is associated with FLD, especially with linguistically mediated executive dysfunction. Particularly, SH for fruity smells may be a sensitive indicator of FLD.

Waiting impulsivity in progressive supranuclear palsy-Richardson's syndrome.

Background: Waiting impulsivity in progressive supranuclear palsy-Richardson's syndrome (PSP-RS) is difficult to assess, and its regulation is known to involve nucleus accumbens (NAc) subregions. We investigated waiting impulsivity using the "jumping the gun" (JTG) sign, which is defined as premature initiation of clapping before the start signal in the three-clap test and compared clinical features of PSP-RS patients with and without the sign and analyzed neural connectivity and microstructural changes in NAc subregions. Materials and methods: A positive JTG sign was defined as the participant starting to clap before the start sign in the three-clap test. We classified participants into the JTG positive (JTG +) and JTG negative (JTG-) groups and compared their clinical features, microstructural changes, and connectivity between NAc subregions using diffusion tension imaging. The NAc was parcellated into core and shell subregions using data-driven connectivity-based methods. Results: Seventy-seven patients with PSP-RS were recruited, and the JTG + group had worse frontal lobe battery (FAB) scores, more frequent falls, and more occurrence of the applause sign than the JTG- group. A logistic regression analysis revealed that FAB scores were associated with a positive JTG sign. The mean fiber density between the right NAc core and right medial orbitofrontal gyrus was higher in the JTG + group than the JTG- group. Discussion: We show that the JTG sign is a surrogate marker of waiting impulsivity in PSP-RS patients. Our findings enrich the current literature by deepening our understanding of waiting impulsivity in PSP patients and introducing a novel method for its evaluation.

Sleep Disorders in Four Patients With Myotonic Dystrophy Type 1.

Sleep disturbances such as excessive daytime sleepiness, central and obstructive sleep apneas, restless legs syndrome, and rapid eye movement sleep dysregulation are prominent in patients with myotonic dystrophy type 1 (DM1). Mild intellectual deficits presented in many patients with DM1. In addition, psychosocial issues caused by neuropsychiatric symptoms are a clinical problem. We herein present the cases of four DM1 patients with sleep disturbances and neuropsychiatric symptoms in the preceding stage of clinically significant muscle symptoms. One of the cases exhibited a sleep disorder and neuropsychiatric symptoms before electromyography showed myotonic discharge, suggesting that careful follow-up is also important. Patients 1 and 2 were first referred to our department due to daytime sleepiness. Patients 3 and 4 were objectively suffering from daytime sleepiness of which they were not subjectively aware of. Patients 1, 3, and 4 obtained high apnea-hypopnea index (AHI) scores, which reflected central and/or obstructive apnea, whereas patient 2 had an AHI score of zero. The daytime cerebrospinal fluid (CSF) orexin levels of all patients ranged from the normal lower limit to low, although they were not as low as those observed in narcolepsy with typical cataplexy. Neuropsychological tests of patients 1 and 2 showed frontal lobe dysfunction. Patients 3 and 4 were diagnosed with mild intellectual disability and autism spectrum disorder, respectively. All patients exhibited indifference toward their own symptoms, which may have resulted from the cognitive decline caused by DM1. Based on family history and/or neurological findings such as myotonia, we suspected DM1 as the cause of their sleep disturbances. Molecular analysis using the triplet repeat-primed polymerase chain reaction (TP PCR) method and Southern blotting, which provided a genetic confirmation of the diagnosis of DM1, were performed. These clinical features of sleep disturbances were unrelated to the length of CTG repeats and are caused by unknown molecular mechanisms. Clinicians should take into account that multisystem involvement in DM1 is hugely variable, and thus, a disabling sleep disorder could overshadow muscle impairment in DM1 patients.

Frontal lobe dysfunction as a predictor of depression and anxiety following temporal lobe epilepsy surgery.

OBJECTIVE: Predictors of psychiatric outcome following TLE surgery have proved elusive and represent a current challenge in the practice of TLE surgery. This prospective study investigated whether frontal lobe dysfunction is predictive of poorer psychiatric outcomes. METHODS: Forty-nine unilateral TLE surgical patients were assessed using the Beck Depression Inventory-Fast Screen (BDI-FS) and Beck Anxiety Inventory (BAI) preoperatively and 6 and 12 months postoperatively. Measures of intellectual function, semantic knowledge, memory and executive function were completed preoperatively, at 6 and 12 months following surgery. RESULTS: Preoperatively, 33 (67%) patients had minimal depressive symptoms, 8 (16%) were mildly depressed, 2 (4%) were moderately depressed, and 6 (12%) reported severe depressive morbidity. Twenty-three (47%) patients reported minimal anxiety, 18 (37%) were mildly anxious, 6 (12%) were moderately anxious and 2 (4%) patients reported severe anxiety symptoms. A mixed-model repeated-measures analysis was performed on the BDI-FS and BAI scores, adjusting for pertinent covariates identified in univariable analyses. At a year following TLE surgery, anxiety symptoms significantly improved but depressive morbidity did not. Indicators of frontal lobe dysfunction moderated the magnitude and direction of mood change. Specifically, pre-surgical cognitive measures of frontal lobe dysfunction predicted increased depression and anxiety symptoms following surgery. There was no relationship between preoperative BDI-FS or BAI scores and seizure outcome at 12 months or change in affective morbidity and seizure outcome. SIGNIFICANCE: This is the first longitudinal study to provide evidence that specific pre-surgical cognitive and behavioural indices of frontal dysfunction are predictive of poorer psychiatric outcome following TLE surgery. In addition, our findings highlight the potential utility of a dysexecutive behavioural rating scale (DEX) as an assessment tool in epilepsy. Examination of executive functioning in pre-surgical evaluations may lead to an increase in the power of prognostic models used to predict the psychiatric outcome of TLE surgery.

Late adult-onset adrenomyeloneuropathy evolving with atypical severe frontal lobe syndrome: Importance of neuroimaging.

X-linked adrenoleukodystrophy (X-ALD) is a rare inherited metabolic disease affecting the nervous system and the adrenal glands. It is caused by a mutation of the ABCD1 gene, resulting in the impaired degradation of very long-chain fatty acids and their subsequent accumulation in several organs and tissues. X-ALD is notable for its high phenotypical variability, that includes isolated adrenocortical insufficiency, slowly progressive myelopathy with paraparesis, ataxia, and peripheral neuropathy to severe childhood cerebral forms. Here, we describe the case of an X-ALD patient with a p.Gly343Val mutation in ABCD1 gene, who presented in adulthood with a spinal syndrome of mild severity, and later developed a progressive cognitive and behavioral syndrome. Our patient showed a striking correlation between clinical phenotype and neuroimaging, including a brain fluoro-2-deoxy-d-glucose positron emission tomography that displayed an atypical cerebral glucose metabolism.

Dysfunctional frontal lobe activity during inhibitory tasks in individuals with childhood trauma: An event-related potential study.

Background: Individuals who experience childhood trauma are vulnerable to various psychological and behavioral problems throughout their lifetime. This study aimed to investigate whether individuals with childhood trauma show altered frontal lobe activity during response inhibition tasks. Methods: In total, 157 healthy individuals were recruited and instructed to perform a Go/Nogo task during electroencephalography recording. Source activities of N2 and P3 of Nogo event-related potentials (ERP) were analyzed. The Childhood Trauma Questionnaire (CTQ) and Barratt Impulsivity Scale (BIS) were applied. Individuals were divided into three groups based on their total CTQ score: low CTQ, middle CTQ, and high CTQ groups. Results: The high CTQ group exhibited significantly higher BIS scores than the low CTQ group. P3 amplitudes of the differences between Nogo and Go ERP waves exhibited higher mean values in the low CTQ than the high CTQ group, with trending effects. In Nogo-P3, the source activities of the right anterior cingulate cortex, bilateral medial frontal cortex (MFC), bilateral superior frontal gyrus (SFG), and right precentral gyrus were significantly lower in the high CTQ than the low CTQ group. Motor impulsivity showed a significant negative correlation with activities of the bilateral MFC and SFG in Nogo-P3 conditions. Conclusions: Our study revealed that individuals with childhood trauma have inhibitory failure and frontal lobe dysfunction in regions related to Nogo-P3.

Reversible Non-parkinsonian Bradykinesia with Impaired Frontal Lobe Function as the Predominant Manifestation of Adrenal Insufficiency.

A 69-year-old Japanese man with a history of suprasellar surgery and irradiation developed bradykinesia and mild fatigue without muscle weakness, myalgia, pyramidal or extrapyramidal signs, parkinsonian symptoms, or ataxia. An endocrinological work-up revealed anterior hypopituitarism associated with secondary adrenal insufficiency. Higher brain function tests indicated an impaired frontal lobe function. The patient's bradykinesia, fatigue, and frontal lobe dysfunction improved within 2 weeks after the initiation of corticosteroid replacement therapy. To our knowledge, this is the first reported case of adrenal insufficiency manifesting as non-parkinsonian bradykinesia. Physicians should consider reversible non-parkinsonian bradykinesia associated with frontal lobe dysfunction as an unusual manifestation of adrenal insufficiency.

[A case of hereditary sensory and autonomic neuropathy type 1E with frontal lobe dysfunction as an initial symptom].

A 49-year-old man had developed gradually personality change, gait disturbance, and hearing loss for five years. On admission, he presented with frontal release signs, stuttering, vertical gaze palsy, sensorineural deafness, muscle rigidity, ataxia, and sensory disturbance with areflexia in the lower extremities. Brain MRI demonstrated atrophy in the cerebellum and midbrain tegmentum as well as cerebral atrophy, predominantly in the frontal lobe. He was tentatively diagnosed as progressive supranuclear palsy on the basis of clinical features and imagings. On nerve conduction study, no sensory nerve action potentials were elicited in the upper and lower extremities. Details of family history revealed a hereditary sensory neuropathy with autosomal dominant inheritance in his relatives. Because genetic analysis showed a rare missense mutation (c.1483T>C, p.Y495H) in DNA methyltransferase 1 gene, we diagnosed him as having hereditary sensory and autonomic neuropathy type 1E (HSAN1E). In addition, p.M232R mutation in prion protein gene was detected. It should be kept in mind that there are some patients with HSAN1E presenting with frontal lobe dysfunction as an initial symptom and with clinical features mimicking progressive supranuclear palsy.

Associations between neuropsychiatric symptoms and cognition in Chinese patients with amyotrophic lateral sclerosis.

Our objective was to explore features of the neuropsychiatric symptoms in Chinese patients with amyotrophic lateral sclerosis (ALS) and the associations between these neuropsychiatric symptoms and cognition. A total of 91 ALS patients were evaluated using three recommended scales including the Neuropsychiatric Inventory (NPI), Addenbrooke's Cognitive Examination Revised (ACE-R), and Frontal Assessment Battery (FAB) tests. The mean age of onset was 52.5 ± 10.8 years. The median NPI score of all patients was 2.0. The most common neuropsychiatric symptom was dysphoria/depression (59.3%), followed by anxiety (41.8%) and irritability/lability (26.4%). There were no significant differences in the frequency of neuropsychiatric symptoms in terms of gender, age of onset, onset form and disease duration. There were no significant differences in NPI total score, ACE-R total score and FAB total score in terms of gender, age of onset, onset form and disease duration, except for a higher ACE-R score observed in patients with a shorter disease duration. The NPI score had a strong correlation with the ACE-R score but not with the FAB score. In conclusion, neuropsychiatric symptoms appear to be quite common in Chinese ALS patients, who were likely to present with the emotional states of depression or anxiety. The neuropsychiatric symptoms in ALS are closely related to global cognition dysfunction.