Sleep apnoea headache in obstructive sleep apnoea syndrome patients presenting with morning headache: comparison of the ICHD-2 and ICHD-3 beta criteria.

BACKGROUND: Morning headache is associated with obstructive sleep apnoea syndrome (OSAS); however, OSAS patients present with various characteristics of morning headache, and they often do not fulfil the International Classification of Headache Disorders (ICHD)-2 criteria for "sleep apnoea headache". The aims of this study were to assess the new ICHD-3 beta criteria for sleep apnoea headache in OSAS patients and to evaluate the differences with the ICHD-2. METHODS: We conducted a cross-sectional survey regarding morning and sleep apnoea headaches that included 235 OSAS outpatients receiving continuous positive airway pressure (CPAP) treatment. The presence of morning headache was evaluated by reviewing the medical records before administration of CPAP treatment. RESULTS: Of all of the OSAS patients, 48 (20.4%) reported morning headaches. Of the 48 patients with morning headaches, 29 (60.4%) and 39 (81.3%) fulfilled the ICHD-2 and ICHD-3 beta criteria for sleep apnoea headache, respectively. The increased frequency of individuals who qualified for diagnosis was likely attributable to the extension of headache duration from 30 min to 4 h. The severity of OSAS was not associated with the presence of sleep apnoea headache. CONCLUSIONS: The utilisation of ICHD-3 beta criteria is clinically useful for diagnosing sleep apnoea headache in patients with OSAS. Applying the ICHD-3 beta criteria was of clinical significance when considering the marked response of these headaches to CPAP therapy. The cause of sleep apnoea headache remains to be elucidated.

Probable rapid eye movement sleep behavior disorder, nocturnal disturbances and quality of life in patients with Parkinson's disease: a case-controlled study using the rapid eye movement sleep behavior disorder screening questionnaire.

BACKGROUND: Increasing evidence provides a clear association between rapid eye movement sleep behavior disorders (RBD) and Parkinson's disease (PD), but the clinical features that determine the co-morbidity of RBD and PD are not yet fully understood. METHODS: We evaluated the characteristics of nocturnal disturbances and other motor and non-motor features related to RBD in patients with PD and the impact of RBD on their quality of life. Probable RBD (pRBD) was evaluated using the Japanese version of the RBD screening questionnaire (RBDSQ-J). RESULTS: A significantly higher frequency of pRBD was observed in PD patients than in the controls (RBDSQ-J ≥ 5 or ≥ 6: 29.0% vs. 8.6%; 17.2% vs. 2.2%, respectively). After excluding restless legs syndrome and snorers in the PD patients, the pRBD group (RBDSQ-J≥5) showed higher scores compared with the non-pRBD group on the Parkinson's disease sleep scale-2 (PDSS-2) total and three-domain scores. Early morning dystonia was more frequent in the pRBD group. The Parkinson's Disease Questionnaire (PDQ-39) domain scores for cognition and emotional well-being were higher in the patients with pRBD than in the patients without pRBD. There were no differences between these two groups with respect to the clinical subtype, disease severity or motor function. When using a cut-off of RBDSQ-J = 6, a similar trend was observed for the PDSS-2 and PDQ-39 scores. Patients with PD and pRBD had frequent sleep onset insomnia, distressing dreams and hallucinations. The stepwise linear regression analysis showed that the PDSS-2 domain "motor symptoms at night", particularly the PDSS sub-item 6 "distressing dreams", was the only predictor of RBDSQ-J in PD. CONCLUSION: Our results indicate a significant impact of RBD co-morbidity on night-time disturbances and quality of life in PD, particularly on cognition and emotional well-being. RBDSQ may be a useful tool for not only screening RBD in PD patients but also predicting diffuse and complex clinical PD phenotypes associated with RBD, cognitive impairment and hallucinations.

Impact of the COVID-19 Pandemic on the Quality of Life of Patients with Parkinson's Disease and Their Caregivers: A Single-Center Survey in Tochigi Prefecture.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has negatively affected the mental health of the general population. OBJECTIVE: We investigated the determinants of quality of life (QOL) in Parkinson's disease (PD) patients during the COVID-19 pandemic. METHODS: Impacts of lifestyle changes due to the COVID-19 pandemic on 100 patients with PD and their caregivers/spouses were assessed. The Hospital Anxiety and Depression Scale was used to assess anxiety and depression. The physical component summary (PCS) and mental component summary (MCS) scores of the short form (SF)-8 were used to evaluate health-related QOL. RESULTS: Regarding health-related QOL, physical function, role physical, general health, vitality and the PCS score were significantly worse in PD patients than in caregivers. Worsening of PD-related symptoms, increased stress, and decreased physical activity were observed in 29.0%, 37.0% and 44.0% of PD patients, respectively. Sixteen patients (16.0%) experienced problems with hospital access, but none reported medication shortages. Strong concerns about COVID-19 were reported by 47.0% of caregivers and 50.0% of PD patients. In PD patients, increased gait disturbance and rigidity, disease severity, smoking, the levodopa equivalent dose and decreased body weight predicted a worse PCS score; anxiety, depression, female sex, stress and long disease duration predicted a worse MCS score. In caregivers, age and smoking contributed to a worse PCS score; depression, stress and worsening patient mood contributed to a worse MCS score. CONCLUSION: We report the negative impacts of the COVID-19 pandemic on health-related QOL and its determinants in PD patients and their caregivers.

Serum uric acid levels in Parkinson's disease and related disorders.

OBJECTIVE: Serum uric acid (UA) levels are reported to be decreased in patients with Parkinson's disease (PD) and multiple system atrophy (MSA). However, clinical correlates of serum UA levels are still unclear in PD-related disorders. We conducted a cross-sectional study to evaluate the associations between serum UA levels and disease duration, disease severity, and motor function among PD, MSA, and progressive supranuclear palsy (PSP) patients. METHODS: A total of 100 patients with PD, 42 patients with MSA, 30 patients with PSP, and 100 controls were included in this study. Serum UA levels were determined, and associations among serum UA levels and disease duration, disease severity, and motor function in PD, PSP, and MSA patients were evaluated. RESULTS: Serum UA levels were significantly lower in male PD, MSA, and PSP patients compared with the controls, but not in female patients. Serum UA levels were negatively correlated with disease duration and severity in MSA and PSP patients, but no correlations were observed in PD patients. The serum UA levels were significantly decreased in the tauopathy group (PSP patients) compared with the synucleinopathy group (PD and MSA patients) after adjusting for age, gender, and body mass index. CONCLUSION: We found decreased serum UA levels in male patients with PD-related disorders (PD, MSA, and PSP) compared with male controls, and significant correlations between serum UA levels and disease severity in MSA and PSP patients.

Characterizing restless legs syndrome and leg motor restlessness in patients with Parkinson's disease: A multicenter case-controlled study.

BACKGROUND: We investigated the prevalence and impact of restless legs syndrome (RLS) and leg motor restlessness (LMR) in patients with Parkinson's disease (PD) in a multicenter study. METHODS: A total of 436 PD patients and 401 age- and sex-matched controls were included in this study. RLS was diagnosed based on four essential features. LMR was diagnosed when a participant exhibited the urge to move his or her legs but did not meet the four essential features of RLS. RESULTS: The RLS prevalence did not differ between PD patients and controls (3.4% vs. 2.7%), while LMR prevalence was significantly higher in PD patients than in controls (12.8% vs. 4.5%). PD patients with RLS or LMR had a higher prevalence of excessive daytime sleepiness (EDS) (50.7%, vs. 6.9%), probable REM sleep behavior disorder (38.0% vs. 3.4%) and PD-related sleep problems (49.3% vs. 20.7%) than controls with RLS or LMR. RLS/LMR preceding PD onset was related to an older age of PD onset. CONCLUSION: Our study revealed an increased prevalence of LMR but not RLS in PD patients. LMR could be an early manifestation of PD; however, whether LMR is within the range of RLS or whether LMR and RLS constitute different entities in PD requires further studies.

A Card-type Odor Identification Test for Japanese Patients with Parkinson's Disease and Related Disorders.

Objective The characteristics of olfactory impairment in Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) have not been determined in detail. We assessed the olfactory function among PD, MSA and PSP patients. Methods A card-type odor identification test, Open Essence (OE, Wako, Japan), which consists of 12 different odorants familiar to Japanese subjects, was administered to 98 PD patients, 32 MSA patients, 17 PSP patients and 96 control subjects ≥50 years of age. Results The PD patients had significantly lower OE scores than the other groups. The OE scores of the MSA and PSP patients fell between those of the PD patients and the control subjects. A cut-off OE score of 6 was beneficial for differentiating PD patients from controls with 84.7% sensitivity and 85.4% specificity. A cut-off OE score of 4 had 60.2% sensitivity and 77.6% specificity for differentiating PD patients from MSA and PSP patients. The correct answer rates for the curry, Japanese orange and perfume odorants in the PD patients were lower than those in the MSA and PSP patients and controls. The PD patients also had the highest ratio of "not detected" choices across the 12 odors. Conclusion Marked olfactory impairment was a feature of the patients with PD, while mild olfactory impairment was observed in those with MSA or PSP. The answer patterns and the specific odorants may also be useful in differentiating PD from related disorders.

Usefulness of Cardiac MIBG Scintigraphy, Olfactory Testing and Substantia Nigra Hyperechogenicity as Additional Diagnostic Markers for Distinguishing between Parkinson's Disease and Atypical Parkinsonian Syndromes.

BACKGROUND: We aimed to evaluate the utility of the combined use of cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy, olfactory testing, and substantia nigra (SN) hyperechogenicity on transcranial sonography (TCS) in differentiating Parkinson's disease (PD) from atypical parkinsonian syndromes (APSs), such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). METHODS: Cardiac MIBG scintigraphy, card-type odor identification testing (Open Essence (OE), Wako, Japan), and TCS were performed with 101 patients with PD and 38 patients with APSs (MSA and PSP). Receiver operating characteristic (ROC) curve analysis was used to assess the sensitivity and specificity of these batteries for diagnosing PD from APSs. The diagnostic accuracy of the three tests was also assessed among patients at the early disease stage (drug-naïve patients with a disease duration of 3 years or less). RESULTS: In differentiating PD from APSs, the area under the ROC curve was 0.74 (95% CI, 0.65-0.83), 0.8 (95% CI, 0.73-0.87), and 0.75 (95% CI, 0.67-0.82) for TCS, cardiac MIBG scintigraphy, and olfactory testing, respectively. The diagnostic sensitivity and specificity were 53.1% and 91.7%, respectively, for TCS, 70.3% and 86.8%, respectively, for cardiac MIBG scintigraphy, 58.4% and 76.3%, respectively, for OE. Among early-stage patients, sensitivity and specificity were 50.0% and 93.8%, respectively, for TCS, 57.1% and 87.5%, respectively, for cardiac MIBG scintigraphy, and 54.8% and 79.2%, respectively, for OE. At least one positive result from 3 tests improved sensitivity (86.1%) but decreased specificity (63.2%). In contrast, at least 2 positive results from 3 tests had good discrimination for both early-stage patients (50.0% sensitivity and 93.8% specificity) and patients overall (57.8% sensitivity and 95.8% specificity). Positive results for all 3 tests yielded 100% specificity but low sensitivity (25%). CONCLUSIONS: At least 2 positive results from among TCS, cardiac MIBG scintigraphy, and olfactory testing can support clinical diagnosis in distinguishing PD from APSs.

Recurrent juvenile ischemic stroke caused by bow hunter's stroke revealed by carotid duplex ultrasonography.

Bow hunter's stroke (BHS) is a rare cause of vertebrobasilar insufficiency due to rotational vertebral artery (VA) occlusion associated with head turning. We report a juvenile patient presenting with recurrent ischemic stroke caused by BHS, which was revealed by carotid duplex ultrasonography. Carotid duplex ultrasonography performed in the neutral position showed normal findings. However, disappearance of end-diastolic blood flow of contralateral VAs was observed with head rotation. Digital subtraction angiography confirmed occlusion at C1/2 levels in the VA contralateral to the head rotation, bilaterally. Importantly, our patient did not recognize the association of head rotation and previous episodes of stroke. We suggest that BHS should be considered in patients with cryptogenic stroke occurring in the vertebrobasilar artery territory.

The Prevalence and Characteristics of Primary Headache and Dream-Enacting Behaviour in Japanese Patients with Narcolepsy or Idiopathic Hypersomnia: A Multi-Centre Cross-Sectional Study.

BACKGROUND: Because the prevalence and characteristics of primary headache have yet to be thoroughly studied in patients with hypersomnia disorders, including narcolepsy and idiopathic hypersomnia, we examined these parameters in the Japanese population. METHODS: In a multicentre cross-sectional survey, among 576 consecutive outpatients with sleep disorders, 68 narcolepsy patients and 35 idiopathic hypersomnia patients were included. Additionally, 61 healthy control subjects participated. Semi-structured headache questionnaires were administered to all participants. RESULTS: The patients with narcolepsy (52.9%) and idiopathic hypersomnia (77.1%) more frequently experienced headache than the healthy controls (24.6%; p<0.0001). The prevalence rates were 23.5%, 41.2% and 4.9% for migraine (p<0.0001) and 16.2%, 23.5% and 14.8% (p = 0.58) for tension-type headache among the narcolepsy patients, the idiopathic hypersomnia patients and the control subjects, respectively. Those who experienced migraine more frequently experienced excessive daytime sleepiness, defined as an Epworth Sleepiness Scale score of ≥10, than those who did not experience headache among the patients with narcolepsy (93.8% vs. 65.6%, p = 0.040) and idiopathic hypersomnia (86.7% vs. 37.5%, p = 0.026). Dream-enacting behaviour (DEB), as evaluated by the rapid eye movement sleep disorders questionnaire, was more frequently observed in the narcolepsy patients than in the idiopathic hypersomnia patients and the control subjects. An increased DEB frequency was observed in the narcolepsy patients with migraines compared to those without headache. CONCLUSIONS: Migraines were frequently observed in patients with narcolepsy and idiopathic hypersomnia. DEB is a characteristic of narcolepsy patients. Further studies are required to assess the factors that contribute to migraines in narcolepsy and idiopathic hypersomnia patients.

Clinical correlates of serum insulin-like growth factor-1 in patients with Parkinson's disease, multiple system atrophy and progressive supranuclear palsy.

BACKGROUND: Recently, increased serum insulin-like growth factor-1 (IGF-1) levels have been reported in patients with Parkinson's disease (PD) and multiple system atrophy (MSA). OBJECTIVE: To assess a correlation between the serum IGF-1 levels and clinical background factors in patients with PD and related disorders such as MSA and progressive supranuclear palsy (PSP). METHODS: A total of 79 PD patients, 25 MSA patients, 16 PSP patients and 52 healthy controls were included in this study. The serum IGF-1 and growth hormone (GH) levels were measured in a fasting state. Unified PD Rating Scale (UPDRS) part III was used to evaluate motor function. Unified MSA Rating Scale (UMSARS) part II was also employed for the MSA patients. RESULTS: The serum IGF-1 levels were significantly increased in the MSA patients compared with the PD patients and controls. No significant differences were observed in the serum GH levels among the patients and controls. The serum IGF-1 levels of PD patients with Hoehn and Yahr stage 2 were significantly higher than those of patients with Hoehn and Yahr stages 3-5. In patients with PD and PSP, the serum IGF-1 levels were negatively correlated with UPDRS part III. In contrast, patients with MSA showed a positive correlation of the serum IGF-1 levels with disease duration, UPDRS part III and UMSARS part II. CONCLUSION: The difference in the serum IGF-1 level and its correlation with clinical variables among these disorders may reflect different ongoing disease processes in each disorder.

Acute hemicerebellitis in a young adult: a case report and literature review.

Acute hemicerebellitis, marked by headache with or without cerebellar signs, is a rare clinical entity involving a unilateral cerebellar hemisphere. The pathogenesis of acute hemicerebellitis remains unclear, and the disease rarely occurs in adults. Here, we report an 18-year-old woman who presented with a lack of coordination of the right hand and leg lasting longer than one week, following a pulsatile headache. A neurological examination disclosed ocular dysmetria, right-sided limb ataxia and slight truncal ataxia. Cerebrospinal fluid analysis showed mononuclear pleocytosis. The serology and autoimmune studies were unremarkable. Brain magnetic resonance imaging (MRI) revealed a focal signal change in the right cerebellar hemisphere and vermis. Acute hemicerebellitis was diagnosed, and the patient was treated with intravenous methylprednisolone sodium succinate and acyclovir. Subsequently, the headache resolved, and the cerebellar signs were markedly improved. Twenty days after admission, she became asymptomatic and brain MRI showed resolution of cerebellar hyperintensity on the right side. In conclusion, we identified only 6 additional patients with adult-onset acute hemicerebellitis from previous reports, highlighting the importance of recognizing this rare clinical entity. Its clinical outcome is usually favorable, but in the acute phase, attention should be directed toward clinical symptoms that are suggestive of increased intracranial pressure.

Does pramipexole treatment improve headache in patients with concomitant migraine and restless legs syndrome?

BACKGROUND: Recent studies have suggested a strong link between migraines and restless legs syndrome (RLS). It is possible that these disorders share a dopaminergic dysfunction in the hypothalamic A11 nucleus that contributes to this association. However, there have been no clinical studies to evaluate the effect of dopaminergic treatment on migraine symptoms in patients with concomitant migraines and RLS. METHODS: We present an illustrative patient with concomitant RLS and migraine who showed improvement in her headache frequency and RLS symptoms following immediate-release pramipexole (P-IR) treatment and provide review results from the medical records of patients who experienced both migraines and RLS in our previous cross-sectional study. RESULTS: Ten patients (nine patients from the previously completed single-center study) received P-IR treatment were included in the study. RLS symptoms improved markedly in all of the subjects. Five out of the 10 patients (50%) reported improvement in migraine headaches. Of these five patients, four (80%) had reported morning headaches before P-IR treatment. DISCUSSION: Our results indicate that the identification of RLS in migraine patients is clinically significant and that dopaminergic treatment may improve both migraines, particularly morning headache (80% improvement in this study), and RLS symptoms. However, further clinical studies are warranted to verify our results.

Snoring is associated with an impaired motor function, disease severity and the quality of life but not with excessive daytime sleepiness in patients with Parkinson's disease.

OBJECTIVE: There are conflicting results regarding the frequency and clinical significance of sleep related breathing disorders in patients with Parkinson's disease (PD). The aim of this study was to investigate the relationship between snoring and its clinical correlates in patients with PD. METHODS: A total of 93 PD patients and 93 controls were analyzed from a previously conducted cross-sectional study. Snoring was defined as a snoring frequency of ≥ 2 days/week (a score of 2 or higher on the PD Sleep Scale-2 subitem 15). Excessive daytime sleepiness (EDS) was defined as an Epworth Sleepiness Scale score of ≥ 10. RESULTS: Snoring was more prevalent in the patients with PD than in the controls (14.0% vs. 1.1%). The PD patients who snored exhibited greater disease severity, worse scores on the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS) and the Parkinson fatigue scale and more impaired scores in several domains of the Parkinson's Disease Questionnaire, including the domains of mobility, activities of daily living, emotional well-being, communication and bodily discomfort, when compared to those who did not snore. No between-group differences were found in EDS. A higher proportion of the UPDRS motor scores for bradykinesia was seen in the PD patients who snored compared to that observed in the PD patients who did not snore. CONCLUSION: We found that snoring was more frequent in PD patients than in controls. Furthermore, snoring in PD patients was associated with disease severity, an impaired motor function and a decreased quality of life, although it was not associated with EDS.

[A 56-year-old woman with adult-onset ophthalmoplegic migraine presenting with recurrent bilateral abducens nerve palsy].

A 56-year-old woman had been experiencing episodic left eye pain followed within 3 days by double vision and adduction of the left eye since the age of 30. The episodes occurred once per month, and her symptoms spontaneously resolved within 3 days. The patient was diagnosed with ophthalmoplegic migraine (OM) with left abducens nerve palsy at the age of 53 years. In May 2011, she developed bilateral retro-orbital pain followed by double vision and limitation of abduction of the right eye. She recalled having a cold and high fever 10 days before the onset of the headache. MRI showed no thickening or enhancement of the right abducens nerve. Constructive interference in steady-state (CISS) MRI showed neurovascular contact between the right abducens nerve and anterior inferior cerebellar artery. Right abducens nerve palsy accompanied by OM was diagnosed after other diseases that can cause ophthalmoplegia were excluded. The patient's eye symptoms gradually improved following steroid treatment. There have been a few similar case reports of adult patients with OM showing left and right abducens nerve palsy at different time points. In this case report, we discuss the possible mechanisms related to OM.

Nocturnal disturbances and restlessness in Parkinson's disease: using the Japanese version of the Parkinson's disease sleep scale-2.

OBJECTIVE: The aim of this study was to assess the validity and the reliability of the Japanese version of the Parkinson's disease sleep scale (PDSS)-2 and to use this scale to identify nocturnal symptoms and their impact on patient's quality of life. METHODS: A cross-sectional, case-controlled study was conducted consisting of 93 patients with Parkinson's disease (PD) and 93 age- and gender-matched control subjects. The Japanese version of the PDSS-2 was used for the evaluation of nocturnal disturbances. The patient's quality of life was evaluated with the Parkinson's Disease Quality of Life questionnaire (PDQ-39) and their depressive symptoms were assessed with the Beck Depression Inventory-II (BDI-II), respectively. In addition, the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and Parkinson Fatigue Scale (PFS) were administered. RESULTS: As assessed using the PDSS-2, PD patients had significantly impaired scores compared with control subjects (15.0±9.7 vs. 9.1±6.6, p<0.001). The ESS, BDI-II and PFS scores were significantly impaired in PD patients compared with controls. A satisfactory internal consistency and test-retest reliability score were obtained for the PDSS-2 total score (Cronbach's alpha=0.86). The PDSS-2 was correlated with the PSQI, ESS, BDI-II, PFS, PDQ-39 summary index, all of the PDQ-39 domains and Unified Parkinson's Disease Rating Scale part III. The frequency of restless legs syndrome (RLS) was not significantly different between PD patients and controls (5.5% vs. 2.2%), but nocturnal restlessness was significantly more frequent in PD patients than controls. Stepwise linear regression analyses revealed the PDQ-39 summary index and the PSQI global score as significant predictors for the PDSS-2 total score. CONCLUSIONS: Our study confirmed the usefulness of the Japanese version of the PDSS-2 that enables the comprehensive assessment of nocturnal disturbances in PD. The association between RLS and nocturnal restlessness in PD requires further study.

Lymphocytic hypophysitis accompanied by aseptic meningitis mimics subacute meningoencephalitis.

A 66-year-old man was admitted to our hospital with muscle pain, fatigue and appetite loss that had lasted for a month. The patient was somnolent and had nuchal stiffness with a high fever. Cerebrospinal fluid (CSF) tests demonstrated lymphocytic pleocytosis with a decreased CSF-blood glucose ratio. The tests for tuberculous, fungal and carcinomatous meningitis and herpetic meningoencephalitis were negative. Endocrinological exams showed hypopituitarism and diabetes insipidus. A pituitary MRI showed an enlargement of the pituitary stalk. A diagnosis of lymphocytic hypophysitis with aseptic meningitis was made after the exclusion of secondary hypophysitis. Lymphocytic hypophysitis with aseptic meningitis can mimic subacute meningoencephalitis.