The Role of Muscle Strength in the Sit-to-Stand Task in Parkinson's Disease.

Background: Rising from a chair or the sit-to-stand (STS) task is frequently impaired in individuals with Parkinson's disease (PD). These patients commonly attribute such difficulties to weakness in the lower extremities. However, the role of muscle strength in the STS transfer task has not been fully elucidated. Objective: We aim at determining the role of muscle strength in the STS task. Methods: We studied 90 consecutive patients with PD and 52 sex- and age-matched controls. Lower limb strength was determined in both legs by clinical examination using the Medical Research Council Scale, dynamometric (leg flexion) and weighting machine (leg pressure) measures. Patients were interrogated regarding the presence of subjective lower limb weakness or allied sensations. Results: There were 20 patients (22.2%) with abnormal STS task (item 3.9 of the MDS-UPDRS-III ≥2 points). These patients had higher modified Hoehn and Yahr stage (P < 0.001) and higher total motor scores of the MDS-UPDRS(P < 0.001), compared with 70 PD patients with normal STS task. Patients with abnormal STS task endorsed lower limb weakness more frequently and had lower muscle strength in the proximal lower extremities, compared to PD patients with normal STS task and normal controls. The presence of perceived lower limb weakness increased the risk of an abnormal STS task, OR: 11.93 (95% C.I. 1.51-94.32), whereas a hip extension strength ≤9 kg/pressure also increased the risk of abnormal STS task, OR: 4.45 (95% C.I. 1.49-13.23). In the multivariate regression analysis, bradykinesia and decreased hip strength were related to abnormal STS task. Conclusions: Patients with PD and abnormal STS task complain more commonly of lower limb weakness and have decreased proximal lower limb strength compared to patients with PD and normal STS task, likely contributing to abnormalities in performing the STS task.

Objective and self-perceived lower limb weakness in Parkinson's disease.

Background: Lower limb weakness is a long-recognized symptom in patients with Parkinson's disease (PD), described by James Parkinson in his seminal report on 'paralysis agitans'. However, little is known on the frequency, clinical correlations, and association with objective decrease in muscle strength in such patients. Objective: The objective of this study was to assess the frequency of objective and perceived lower limb weakness in patients with PD. Methods: We studied 90 consecutive patients with PD and 52 age-matched controls. We recorded clinical and demographic variables, as well as perceived weakness and allied abnormal lower limb sensations, including 'heavy legs', 'fatigued legs', and 'pain'. Symptoms consistent with restless legs syndrome were not considered. Lower limb strength was determined in both legs by means of the Medical Research Council scale, dynamometric (leg flexion) and weighting machine (leg pressure) measures. Results: Weakness and allied abnormal lower limb sensations were reported in 69% of patients with PD and 21% of healthy controls. Patients with PD had decreased leg pressure compared with healthy controls (p = 0.002). Among patients with PD, an association between perceived leg weakness (and allied sensations) and gait freezing (p = 0.001) was observed in the multivariate regression analysis; however, these variables only explained 30.4% of the variance. Moreover, PD patients with and without abnormal lower limb sensations had similar muscle strength by objective measurements. Conclusion: Perceived lower limb weakness and allied abnormal sensations are common in patients with PD. However, there is a dissociation between perceived weakness and objective muscle strength in the lower limbs. These abnormal sensations were mostly related to gait freezing but a causal association is questionable.

Intestinal Decontamination Therapy for Dyskinesia and Motor Fluctuations in Parkinson's Disease.

Parkinson's disease is neurodegenerative disorder with an initial robust response to levodopa. As the disease progresses, patients frequently develop dyskinesia and motor fluctuations, which are sometimes resistant to pharmacological therapy. In recent years, abnormalities in gut microbiota have been identified in these patients with a possible role in motor manifestations. Dysbiosis may reduce levodopa absorption leading to delayed "On" or "no-On" states. Among 84 consecutive patients with PD, we selected 14 with levodopa-induced dyskinesia and motor fluctuations with a Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part IV ≥ 8 points following a trial of pharmacological adjustment 2-3 months prior to study enrollment or adjustments in deep brain stimulation therapy. Patients received treatment with sodium phosphate enema followed by oral rifaximin and polyethylene glycol for 7 and 10 days, respectively. Evaluations between 14 to 21 days after starting treatment showed improvement in MDS-UPDRS-IV (P = 0.001), including duration (P = 0.001) and severity of dyskinesia (P = 0.003); duration of medication "Off"-state (P = 0.004); functional impact of motor fluctuations (P = 0.047) and complexity of motor fluctuations (P = 0.031); no statistical improvement was observed in "Off" dystonia (P = 0.109) and total motor scores (P = 0.430). Marked to moderate improvement in dyskinesia was observed in 57% of cases with blinded evaluation of videos. About 80% of patients perceived moderate to robust improvement at follow-up. A therapeutic strategy aimed at decontamination of intestines showed benefit in motor fluctuations and dyskinesia. Further studies should confirm and clarify the mechanism of improvement observed in these patients.

Functional (Psychogenic) Movement Disorders Presenting During Sleep.

Background: Functional (psychogenic) movement disorders are involuntary movements that seems to originate from activation of voluntary motor pathways in the brain. The movements typically present during the waking hours with variable frequency. Case presentation: We present the case of a 24-year-old woman with FMDs during the waking state, but also during stages 1 and 2 of non-REM sleep and REM sleep, recorded with polysomnography. Such movements caused arousal leading to excessive daytime sleepiness and fatigue. Conclusions: FMDs may disrupt sleep causing day time somnolence, adding morbidity to the disorder.

Impulse Control Disorders in Parkinson's Disease: Epidemiology, Pathogenesis and Therapeutic Strategies.

Impulse control disorders (ICDs) in Parkinson's disease (PD) are aberrant behavior such as pathological gambling, hypersexuality, binge eating, and compulsive buying, which typically occur as a result of dopaminergic therapy. Numerous studies have focused on the broad spectrum of ICDs-related behaviors and their tremendous impact on patients and their family members. Recent advances have improved our understanding of ICDs. In this review, we discuss the epidemiology, pathogenesis and treatment of ICDs in the setting of PD.

Anti-Gravity Treadmill Training for Freezing of Gait in Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor impairment. Freezing of gait, impaired mobility and falls are common problems in these patients. We aimed to evaluate the effect of a novel therapy for these patients. METHODS: We studied patients with moderate to severe freezing of gait who underwent antigravity treadmill training twice a week for 4 consecutive weeks with 50% reduction of body weight. RESULTS: We enrolled 26 consecutive patients with PD, 19 completed the study. There were 10 males; mean age at evaluation was 72.7 ± 10.1 years. Compared to baseline, patients showed improvement in the Freezing of Gait Questionnaire (p = 0.001); and a mean reduction of 7 s in the Timed Up & Go (TUG) test (p = 0.004). Moderate or significant improvement in gait was reported by 84% of patients. CONCLUSIONS: Antigravity treadmill training improved freezing of gait and mobility in patients with PD.

Abdominal Wall Dyskinesia: Case Report.

The clinical presentation of repetitive choreiform involuntary movements of the anterior abdominal wall was first introduced as "belly dancer's dyskinesia." Etiologies of this rare condition include idiopathic causes, medication inducement, or post-abdominal surgery. We report a case of orobuccal stereotypic movements and abdominal wall dyskinesia secondary to prochlorperazine intake. The movements began 2 weeks after cessation of prochlorperazine. The patient took this dopamine receptor-blocking medication for 6 months to treat nausea due to chemotherapy. To our knowledge, abdominal wall dyskinesia as a tardive syndrome of prochlorperazine has not been previously reported.

Evaluation of osteoarthritis knee and hip quality of life (OAKHQoL): adaptation and validation of the questionnaire in the Hungarian population.

BACKGROUND: At least 17% of the population suffers from osteoarthritis (OA) in Hungary, according to the European Health Interview Survey. In Hungary, until now there was no OA-specific questionnaire available for the lower limb, in order to monitor the health-related quality of life (HRQoL). This gap gave the relevance of this research. The aim of the study was to perform the Hungarian cross-cultural adaptation and validation of the French-developed Osteoarthritis Knee and Hip Quality of Life (OAKHQoL) questionnaire. METHODS: The five-step translation procedure of the original OAKHQoL was performed by the expert panel and the translators. The created Hungarian version (OAKHQoL-HUN) was tested in six different geographical areas of Hungary. The validity and the reliability of this adapted tool was analyzed by our research group. RESULTS: A total of 99 patients completed the questionnaires (78 women and 21 men), with the average age of 66.6 years (standard deviation (SD) 12.1), living with OA for more than 10 years. Excellent internal consistency was observed in the following domains: physical activity (α = 0.93), mental health (α = 0.91) and pain (α = 0.89). Good correlation was determined between physical subscales (r = 0.615-0.676) and mental subscales (r = 0.633-0.643) compared to generic quality of life instruments (World Health Organization Quality of life - BREF questionnaire and EQ-5D-3L). CONCLUSION: The OAKHQoL-HUN is the first valid and reliable tool for measuring the Hungarian lower limb OA patients' quality of life. TRIAL REGISTRATION: This study is registered (24950-3/2016/EKU) by the National Ethics Committee: the Hungarian Medical Research Council.

Clinical correlations of striatal hand deformities in Parkinson's disease.

BACKGROUND: Hand deformities have been recognized since the 19th century as part of the postural abnormalities observed in Parkinson's disease (PD). However, their pathogenesis and clinical correlations are poorly understood. METHODS: We evaluated 104 hands of 52 consecutive patients with PD by high-resolution photographs taken from the radial aspect of each hand; the degree of flexion of the 2nd metacarpophalangeal (MCP) joint was measured by software. The presence of classical striatal hand deformity (CSHD) was also evaluated, defined as MCP flexion, proximal interphalangeal joint extension, and distal interphalangeal joint flexion. RESULTS: Patients with PD had a mean age of 63.3 ± 12.7 years, and 29 (56%) were male. The degree of MCP joint flexion in both hands showed moderate correlation with the MDS-UPDRS-III motor score (r = 0.518, P < 0.001), mainly related to ipsilateral rigidity and ipsilateral bradykinesia scores, and fair correlation with the Hoehn-Yahr stage. A CSHD only correlated with a younger age at onset of PD (P = 0.049). These hand deformities were not markers of dyskinesia, levodopa equivalent dose, or cognitive dysfunction. CONCLUSIONS: Metacarpophalangeal joint flexion is the most common hand deformity in PD and correlates with rigidity and bradykinesia. A CSHD was only related to a younger age at onset.

The frequency and diagnostic accuracy of hand deformities in Parkinson's disease.

Hand deformities are well-known abnormalities observed in patients with Parkinson's disease (PD). We determined the frequency and diagnostic accuracy of hand deformities in PD. We studied 44 consecutive patients with PD, 44 age- and gender-matched normal controls and 22 patients with essential tremor (ET). By means of photographs taken in both hands of all participants, the degree of metacarpophalangeal (MCP) joint flexion was quantified by software and by blinded evaluations using a semiquantitative scale from the radial aspect, we grouped hands into four grades. The presence of classical striatal hand deformity (CSHD), defined as MCP joint flexion, proximal interphalangeal joint extension and distal interphalangeal joint flexion was also evaluated. Patients with PD had a higher frequency of MCP joint flexion and CSHD compared to normal controls and patients with ET. Mean MCP joint flexion was higher in both hands in patients with PD: 20.8° vs. normal controls (3.3°-3.9°) and patients with ET (2.8°-6.3°), P = 0.001. Concordance between evaluators for MCP joint flexion was fair: κ = 0.34 (P < 0.001), but poor for CSHD: κ = 0.142-0.235 (P < 0.05). A right hand MCP joint flexion of 12.5° and left hand of 10.5°, showed similar sensitivity (0.70) and specificity (between 0.75 and 0.80) than any degree of MCP joint flexion for the diagnosis of PD. CSHD had a sensitivity (0.60-0.80) and specificity (0.78-0.98) for the diagnosis of PD. Hand deformities are commonly observed in patients with PD, they may aid in the diagnosis of PD when compared to normal controls and patients with ET.

Recognizing uncommon presentations of psychogenic (functional) movement disorders.

BACKGROUND: Psychogenic or functional movement disorders (PMDs) pose a challenge in clinical diagnosis. There are several clues, including sudden onset, incongruous symptoms, distractibility, suggestibility, entrainment of symptoms, and lack of response to otherwise effective pharmacological therapies, that help identify the most common psychogenic movements such as tremor, dystonia, and myoclonus. METHODS: In this manuscript, we review the frequency, distinct clinical features, functional imaging, and neurophysiological tests that can help in the diagnosis of uncommon presentations of PMDs, such as psychogenic parkinsonism, tics, and chorea; facial, palatal, and ocular movements are also reviewed. In addition, we discuss PMDs at the extremes of age and mass psychogenic illness. RESULTS: Psychogenic parkinsonism (PP) is observed in less than 10% of the case series about PMDs, with a female-male ratio of roughly 1:1. Lack of amplitude decrement in repetitive movements and of cogwheel rigidity help to differentiate PP from true parkinsonism. Dopamine transporter imaging with photon emission tomography can also help in the diagnostic process. Psychogenic movements resembling tics are reported in about 5% of PMD patients. Lack of transient suppressibility of abnormal movements helps to differentiate them from organic tics. Psychogenic facial movements can present with hemifacial spasm, blepharospasm, and other movements. Some patients with essential palatal tremor have been shown to be psychogenic. Convergence ocular spasm has demonstrated a high specificity for psychogenic movements. PMDs can also present in the context of mass psychogenic illness or at the extremes of age. DISCUSSION: Clinical features and ancillary studies are helpful in the diagnosis of patients with uncommon presentations of psychogenic movement disorders.

Gradenigo syndrome: unusual consequence of otitis media.

INTRODUCTION: In 1904, Giuseppe Gradenigo published his case series on the triad of ipsilateral abducens nerve palsy, facial pain in the trigeminal nerve distribution, and suppurative otitis media, which would subsequently be referred to as Gradenigo syndrome. CASE REPORT: Our patient was a 36-year-old female, 23 weeks pregnant, with a 6-day history of right-sided otalgia and hearing loss and a 4-day history of purulent otorrhea, who presented with severe, holocephalic headache, meningeal signs, fever, photophobia, and mental status decline. Lumbar puncture yielded a white blood cell count of 1,559 cells/mm(3) with 95% polymorphonuclear leukocytes, a red blood cell count of 111 cells/mm(3), a protein level of 61 mg/dl, and a glucose level of <40 mg/dl. Cerebrospinal fluid Gram stain showed Gram-positive diplococci, which were subsequently identified as Streptococcus pneumoniae and treated with ceftriaxone. On the second hospital day, she developed horizontal diplopia due to right abducens nerve palsy and right mydriasis. Both symptoms resolved on the third hospital day. Erosion of temporal bone and opacification of mastoid air cells was shown on CT scan. A CT venogram showed an irregularity of the left transverse and superior sagittal sinuses. She was treated with enoxaparin for possible sinus thrombosis. DISCUSSION: This case demonstrates rare but serious sequelae of otitis media and Gradenigo syndrome. Holocephalic headache from meningitis masked trigeminal pain. Involvement of the ipsilateral petrous apex and surrounding structures on imaging and clinical improvement with antibiotic treatment supports Gradenigo syndrome over intracranial hypertension due to venous sinus thrombosis as the cause of the abducens nerve palsy.

Genome-wide analysis captures the determinants of the antibiotic cross-resistance interaction network.

Understanding how evolution of antimicrobial resistance increases resistance to other drugs is a challenge of profound importance. By combining experimental evolution and genome sequencing of 63 laboratory-evolved lines, we charted a map of cross-resistance interactions between antibiotics in Escherichia coli, and explored the driving evolutionary principles. Here, we show that (1) convergent molecular evolution is prevalent across antibiotic treatments, (2) resistance conferring mutations simultaneously enhance sensitivity to many other drugs and (3) 27% of the accumulated mutations generate proteins with compromised activities, suggesting that antibiotic adaptation can partly be achieved without gain of novel function. By using knowledge on antibiotic properties, we examined the determinants of cross-resistance and identified chemogenomic profile similarity between antibiotics as the strongest predictor. In contrast, cross-resistance between two antibiotics is independent of whether they show synergistic effects in combination. These results have important implications on the development of novel antimicrobial strategies.

Antagonism between bacteriostatic and bactericidal antibiotics is prevalent.

Combination therapy is rarely used to counter the evolution of resistance in bacterial infections. Expansion of the use of combination therapy requires knowledge of how drugs interact at inhibitory concentrations. More than 50 years ago, it was noted that, if bactericidal drugs are most potent with actively dividing cells, then the inhibition of growth induced by a bacteriostatic drug should result in an overall reduction of efficacy when the drug is used in combination with a bactericidal drug. Our goal here was to investigate this hypothesis systematically. We first constructed time-kill curves using five different antibiotics at clinically relevant concentrations, and we observed antagonism between bactericidal and bacteriostatic drugs. We extended our investigation by performing a screen of pairwise combinations of 21 different antibiotics at subinhibitory concentrations, and we found that strong antagonistic interactions were enriched significantly among combinations of bacteriostatic and bactericidal drugs. Finally, since our hypothesis relies on phenotypic effects produced by different drug classes, we recreated these experiments in a microfluidic device and performed time-lapse microscopy to directly observe and quantify the growth and division of individual cells with controlled antibiotic concentrations. While our single-cell observations supported the antagonism between bacteriostatic and bactericidal drugs, they revealed an unexpected variety of cellular responses to antagonistic drug combinations, suggesting that multiple mechanisms underlie the interactions.

Xeroderma pigmentosum/de sanctis-cacchione syndrome: unusual cause of ataxia.

INTRODUCTION: Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder of DNA repair, with a prevalence of 1 in 1 million. It may also be a cause of neurological symptoms including sensorineural hearing loss, peripheral neuropathy, ataxia, and chorea. Severe neurological symptoms including mental retardation, short stature, and hypogonadism invoke De Sanctis-Cacchione syndrome (DCS). CASE REPORT: The patient was a 55-year-old woman with a history of mental retardation who developed chorea at age 32 and ataxia at age 37. She had numerous facial scars from 10 prior basal cell carcinoma excisions as well as diminished deep tendon reflexes, bilateral hearing loss, dysphagia, and skin freckling. Brain MRI revealed severe cortical, cerebellar, and brainstem atrophy. Supportive treatment and prevention of further damage from UV light is the mainstay of treatment in XP and DCS. CONCLUSION: XP and related disorders should be considered in the setting of neurological disorder and multiple cutaneous cancers.

Intracranial hemorrhage in patient treated with rivaroxaban.

Rivaroxaban is an oral factor Xa inhibitor used for stroke prevention in atrial fibrillation. There are currently no evidence-based guidelines for the treatment of hemorrhagic side effects of factor Xa inhibitors. We report a case of a thalamic hemorrhage in an 84 year-old right-handed female on rivaroxaban for treatment of atrial fibrillation. The patient had fallen down steps and became unresponsive. She was found to have diffuse scattered acute subarachnoid hemorrhage as well as intraventricular hemorrhage. Neurosurgical intervention was not required in this case, but controversy over decision making to pursue pro-coagulant therapy in the setting of worsening hemorrhage requiring emergent surgery is discussed.

The safety and efficacy of thalamic deep brain stimulation in essential tremor: 10 years and beyond.

BACKGROUND: Deep brain stimulation (DBS) has proven to be a safe and effective therapy for refractory essential tremor, but information regarding long-term outcomes is lacking. OBJECTIVES: We aimed to assess the long-term safety and efficacy of DBS in patients with essential tremor. METHODS: Patients treated with DBS for essential tremor for at least 8 years were evaluated in the 'on' and 'off' state using the Fahn-Tolosa-Marin tremor rating scale, and their medical records were reviewed to assess complications related to this therapy. RESULTS: We studied 13 patients (7 men): median age at evaluation 79 years (range 47-88), median age at electrode implantation 68 years (range 37-78) and mean time since electrode implantation 132.54±15.3 months (range 114-164). The difference between the 'off' and 'on' state on the motor items of the tremor rating scale was 41.9% (58.62 vs. 34.08, p<0.001) in the non-blinded and 37.2% (56.07 vs. 35.23, p<0.001) in the blinded rating. DBS provided a functional improvement of 31.7% in the 'on' state (15.07 vs. 22.07, p<0.001). A total non-blinded improvement in the tremor rating scale of 39% was observed in the 'on' state (49.15 vs. 80.69, p<0.001). Dysarthria and disequilibrium were common in patients with bilateral stimulation. A DBS-related surgery (electrode revision or internal pulse generator exchange) was necessary on average every 47.9 months to continue with the DBS therapy. CONCLUSIONS: Thalamic DBS is a safe and effective therapy in patients with essential tremor followed for up to 13 years.

Upper facial chorea in Huntington disease.

To provide a systematic description of component movements of upper facial chorea in Huntington disease, consecutive videos of 25 active patients with confirmed diagnosis were scored on eye opening, eye closing, and procerus/corrugator contractions. Of the 25 patients evaluated, 76% exhibited intermittently widened palpebral fissures associated with frontalis contractions. Brief periods of repetitive but irregular blinking were observed in 16%. 8% had brief spasms of the orbital portion of the orbicularis oculi muscles. In addition, brief contractions of procerus and corrugator supercilii muscles were noted in 52%.

Bacterial evolution of antibiotic hypersensitivity.

The evolution of resistance to a single antibiotic is frequently accompanied by increased resistance to multiple other antimicrobial agents. In sharp contrast, very little is known about the frequency and mechanisms underlying collateral sensitivity. In this case, genetic adaptation under antibiotic stress yields enhanced sensitivity to other antibiotics. Using large-scale laboratory evolutionary experiments with Escherichia coli, we demonstrate that collateral sensitivity occurs frequently during the evolution of antibiotic resistance. Specifically, populations adapted to aminoglycosides have an especially low fitness in the presence of several other antibiotics. Whole-genome sequencing of laboratory-evolved strains revealed multiple mechanisms underlying aminoglycoside resistance, including a reduction in the proton-motive force (PMF) across the inner membrane. We propose that as a side effect, these mutations diminish the activity of PMF-dependent major efflux pumps (including the AcrAB transporter), leading to hypersensitivity to several other antibiotics. More generally, our work offers an insight into the mechanisms that drive the evolution of negative trade-offs under antibiotic selection.

Paroxysmal nonkinesigenic dyskinesia with tremor.

Introduction. Paroxysmal nonkinesigenic dyskinesia (PNKD) consists of episodes of chorea, athetosis, or dystonia which are not triggered by movement, with complete remission between episodes. A case of genetically confirmed PNKD with simultaneous tremor has not been previously reported. Case Report. The patient is an 86-year-old right-handed female who presented with episodic stiffness, with onset at age 9. Attacks have a prodrome of difficulty in speaking, followed by abnormal sensation in extremities. Episodes consist of dystonia of trunk associated with upper and lower extremity chorea. There is complete resolution between attacks except for persistent mild head tremor and action tremor of both extremities. Attack frequency and duration as well as tremor amplitude escalated two and a half years ago, in correlation with development of breast carcinoma. Episodes improved after successful cancer treatment, but higher amplitude tremor persisted. There is an autosomal dominant family history of similar episodes but not tremor. Genetic diagnosis was confirmed via A7V mutation of the myofibrillogenesis regulator (MR-1) gene. Conclusion. Exacerbation due to another medical or psychiatric condition should be considered if there is unexpected deterioration in episode frequency or length. PNKD due to MR-1 mutation may exist even in the presence of action tremor.