Physiotherapy for freezing of gait in Parkinson's disease: a systematic review and meta-analysis. / Fisioterapia para la congelación de la marcha en la enfermedad de Parkinson: revisión sistemática y metaanálisis.

INTRODUCTION: Freezing of gait (FOG) is one of the most severe symptoms associated with Parkinson's disease (PD). Physiotherapy treatment could be an effective strategy for treating FOG, but no systematic review has been carried out in this regard. AIM: To identify the characteristics, methodological quality, and main outcomes of the studies that have analyzed the effects of physiotherapy interventions in FOG up to date, by performing a systematic review and a meta-analysis. PATIENTS AND METHODS: Four electronic databases were searched in order to find randomized controlled trials that provided information regarding the effects of any kind of physiotherapy treatment on FOG. The methodological quality of the included investigations was assessed by means of the PEDro scale. RESULTS: Twelve studies were identified for inclusion into the qualitative analysis, with four randomized controlled trials included in the final meta-analysis. The quality of the trials was generally good. Those physiotherapy modalities including cues were more effective for treating FOG than traditional physiotherapy approaches. The meta-analysis indicated that physiotherapy interventions had a significantly greater impact on FOG than control comparisons. CONCLUSIONS: Physiotherapy treatment, especially those modalities including visual and auditory cueing, should be prescribed to PD patients with FOG. Future studies including PD patients with cognitive impairment and FOG objective measurement tools are need to complete the existing scientific evidence.

TITLE: Fisioterapia para la congelación de la marcha en la enfermedad de Parkinson: revisión sistemática y metaanálisis.Introducción. La congelación de la marcha (CDM) es uno de los síntomas más graves asociados con la enfermedad de Parkinson (EP). El tratamiento fisioterapéutico podría ser una estrategia efectiva para su tratamiento, pero no se ha realizado ninguna revisión sistemática al respecto. Objetivo. Identificar las características, la calidad metodológica y los principales resultados de los estudios que han analizado los efectos de las intervenciones fisioterapéuticas en CDM hasta la fecha, mediante la realización de una revisión sistemática y un metaanálisis. Pacientes y métodos. Se realizaron búsquedas en cuatro bases de datos electrónicas para encontrar ensayos controlados aleatorizados que proporcionaran información con respecto a los efectos de cualquier tipo de tratamiento fisioterapéutico sobre la CDM. La calidad metodológica de las investigaciones se evaluó mediante la escala PEDro. Resultados. Se identificaron 12 estudios para su inclusión en el análisis cualitativo y cuatro ensayos controlados aleatorizados se incluyeron en el metaanálisis final. La calidad de los ensayos fue generalmente buena. Las modalidades de fisioterapia que incluían señales fueron más efectivas para tratar la CDM que los enfoques de fisioterapia tradicionales. El meta­análisis indicó que las intervenciones fisioterapéuticas tuvieron un impacto significativamente mayor sobre la CDM que las comparaciones de control. Conclusiones. El tratamiento fisioterapéutico, especialmente las modalidades que incluyen señales visuales y auditivas, debe prescribirse a los pacientes con EP con CDM. Se necesitan estudios futuros que incluyan pacientes con EP con deterioro cognitivo y herramientas de medición objetiva de la CDM para completar la evidencia científica existente.

Personality and Motoric Cognitive Risk Syndrome.

OBJECTIVES: To examine whether five major personality traits are related to the motoric cognitive risk (MCR) syndrome, a pre-dementia syndrome characterized by cognitive complaints and slow gait speed. DESIGN: Cross-sectional. SETTING: Health and Retirement Study (HRS) and the National Health and Aging Trends Survey (NHATS). PARTICIPANTS: Dementia-free older adults aged 65 to 107 years (N > 8000). MEASUREMENTS: In both samples, participants provided data on personality, cognitive complaints, and measures of gait speed, as well as on demographic factors, physical activity, depressive symptoms, and body mass index (BMI). RESULTS: Across the two samples and a meta-analysis, higher neuroticism was related to higher risk of MCR (combined odds ratio [OR] = 1.32; 95% confidence interval [CI] = 1.21-1.45; P < .001), whereas higher extraversion (combined OR = .71; 95% CI = .65-.79; P < .001) and conscientiousness (combined OR = .70; 95% CI = .62-.78; P < .001) were associated with a lower likelihood of MCR. Higher openness was also related to a lower risk of MCR in the HRS and the meta-analysis (combined OR = .77; 95% CI = .70-.85; P < .001), whereas agreeableness was protective only in the HRS (OR = .83; 95% CI = .74-.92; P < .001). Additional analyses indicated that physical activity, depressive symptoms, and BMI partially accounted for these associations. CONCLUSION: This study adds to existing research on the factors related to the risk of MCR by showing an association with personality traits. Personality assessment may help to identify individuals who may be targeted by interventions focused on reducing the risk of MCR and ultimately of dementia. J Am Geriatr Soc 68:803-808, 2020.

Clinicopathologic subtype of Alzheimer's disease presenting as corticobasal syndrome.

INTRODUCTION: The corticobasal syndrome (CBS) is associated with several neuropathologic disorders, including corticobasal degeneration and Alzheimer's disease (AD). METHOD: In this report, we studied 43 AD patients with CBS (AD-CBS) and compared them with 42 AD patients with typical amnestic syndrome (AD-AS), as well as 15 cases of corticobasal degeneration and CBS pathology. RESULTS: Unlike AD-AS, AD-CBS had prominent motor problems, including limb apraxia (90%), myoclonus (81%), and gait disorders (70%). Alien limb phenomenon was reported in 26% and cortical sensory loss in 14%. Language problems were also more frequent in AD-CBS, and memory impairment was less frequent. AD-CBS had more tau pathology in perirolandic cortices but less in superior temporal cortex than AD-AS. In addition, AD-CBS had greater neuronal loss in the substantia nigra. DISCUSSION: AD-CBS is a clinicopathological subtype of AD with an atypical distribution of Alzheimer-type tau pathology. Greater neuronal loss in the substantia nigra may contribute to Parkinsonism which is not a feature of typical AD.

Gait in normal pressure hydrocephalus: characteristics and effects of the CSF tap test.

INTRODUCTION: Normal pressure hydrocephalus (NPH), described by Hakim and Adams in 1965, is characterized by gait apraxia, urinary incontinence, and dementia. It is associated with normal cerebrospinal fluid (CSF) pressure and ventricular dilation that cannot be attributed to cerebral atrophy. OBJECTIVES: To evaluate gait characteristics in patients with idiopathic NPH and investigate the effect of the CSF tap test (CSF-TT) on gait. METHODS: Twenty-five patients diagnosed with probable idiopathic NPH were submitted to the CSF-TT. The procedure aimed to achieve changes in gait parameters. RESULTS: Fifteen gait parameters were assessed before and after the CSF-TT. Five showed a statistically significant improvement (p < 0.05): walking speed (p < 0.001), cadence (p < 0.001), step length (p < 0.001), en bloc turning (p = 0.001), and step height (p = 0.004). CONCLUSION: This study demonstrated that gait speed was the most responsive parameter to the CSF-TT, followed by cadence, step length, en bloc turning, and step height.

Gait in normal pressure hydrocephalus: characteristics and effects of the CSF tap test / Marcha na hidrocefalia de pressão normal: características e efeitos do tap-test

ABSTRACT Normal pressure hydrocephalus (NPH), described by Hakim and Adams in 1965, is characterized by gait apraxia, urinary incontinence, and dementia. It is associated with normal cerebrospinal fluid (CSF) pressure and ventricular dilation that cannot be attributed to cerebral atrophy. Objectives: To evaluate gait characteristics in patients with idiopathic NPH and investigate the effect of the CSF tap test (CSF-TT) on gait. Methods: Twenty-five patients diagnosed with probable idiopathic NPH were submitted to the CSF-TT. The procedure aimed to achieve changes in gait parameters. Results: Fifteen gait parameters were assessed before and after the CSF-TT. Five showed a statistically significant improvement (p < 0.05): walking speed (p < 0.001), cadence (p < 0.001), step length (p < 0.001), en bloc turning (p = 0.001), and step height (p = 0.004). Conclusion: This study demonstrated that gait speed was the most responsive parameter to the CSF-TT, followed by cadence, step length, en bloc turning, and step height.

RESUMO A hidrocefalia de pressão normal (HPN), descrita por Hakim-Adams em 1965, caracteriza-se por apraxia de marcha, incontinência urinária e demência e está associada com pressão normal do líquido cefalorraquidiano e dilatação ventricular não atribuída a atrofia cerebral. Objetivos: Avaliar as características da marcha em pacientes com HPN idiopática e o efeito do "tap-test" (TT) na marcha. Métodos: Vinte e cinco pacientes com o diagnóstico HPN idiopática provável, foram avaliados com o TT. O procedimento tem como objetivo causar mudanças nas características da marcha. Resultados: Quinze parâmetros da marcha foram avaliados com o TT. Cinco mostraram melhora estatisticamente significativa (p < 0,05): velocidade da marcha (p < 0,001), cadência (p < 0,001), comprimento do passo (p < 0,001), giro em "bloco" (p = 0,001) e altura do passo (p = 0,004). Conclusão: Este estudo demonstrou que a velocidade da marcha foi o parâmetro que mais respondeu ao efeito do TT, seguido da cadência, comprimento do passo, giro em "bloco" e altura do passo.

Balance impairment does not necessarily coexist with gait apraxia in mild and moderate Alzheimer's disease.

OBJECTIVES: To assess correlations among gait apraxia, balance impairment and cognitive performance in mild (AD1, n = 30) and moderate (AD2, n = 30) AD. METHOD: The following evaluations were undertaken: gait apraxia (Assessment Walking Skills); balance performance (Berg Balance Scale); Clinical Dementia Rating and Mini-mental State Examination (MMSE). RESULTS: While disregarding AD subgroups, Berg Balance Scale and the MMSE correlated significantly with Assessment Walking Skills and 23% of all subjects scored below its cut-off. After stratification, Berg Balance Scale correlated significantly with Assessment Walking Skills in both AD subgroups, and with the MMSE only in AD1. CONCLUSIONS: Balance impairment does not necessarily coexist with gait apraxia. Gait apraxia is more prevalent in moderate AD when compared with mild AD.

Balance impairment does not necessarily coexist with gait apraxia in mild and moderate Alzheimer's disease / Comprometimento do equilíbrio e apraxia da marcha não necessariamente coexistem na doença de Alzheimer leve e moderada

ABSTRACT Currently, there are no studies reporting how much balance impairment coexists with gait apraxia in mild and moderate Alzheimer’s disease (AD). Objectives To assess correlations among gait apraxia, balance impairment and cognitive performance in mild (AD1, n = 30) and moderate (AD2, n = 30) AD. Method The following evaluations were undertaken: gait apraxia (Assessment Walking Skills); balance performance (Berg Balance Scale); Clinical Dementia Rating and Mini-mental State Examination (MMSE). Results While disregarding AD subgroups, Berg Balance Scale and the MMSE correlated significantly with Assessment Walking Skills and 23% of all subjects scored below its cut-off. After stratification, Berg Balance Scale correlated significantly with Assessment Walking Skills in both AD subgroups, and with the MMSE only in AD1. Conclusions Balance impairment does not necessarily coexist with gait apraxia. Gait apraxia is more prevalent in moderate AD when compared with mild AD.

RESUMO Apraxia da marcha e desequilíbrio são condições subinvestigadas na doença de Alzheimer (DA) leve e moderada. Objetivo Verificar a correlação da apraxia da marcha com desequilíbrio e cognição em 30 idosos com DA leve (DA1) e 30 idosos com DA moderada (DA2). Método Foram feitas as seguintes avaliações: apraxia da marcha (Assessment Walking Skills); equilíbrio (Berg Balance Scale); Clinical Dementia Rating e Mini-exame do estado mental – MEEM. Resultados Desconsiderando-se os grupos, Berg Balance Scale e MEEM correlacionaram-se significativamente com a Assessment Walking Skills, enquanto 23% dos participantes pontuaram abaixo da note de corte da mesma. Considerando-se os grupos, Berg Balance Scale correlacionou-se significativamente com a Assessment Walking Skills em ambos os grupos, embora o MEEM o tenha feito apenas em DA1. Conclusões Desequilíbrio e apraxia da marcha não necessariamente coexistem com apraxia da marcha. Prevalência de apraxia da marcha foi maior na DA moderada do que na DA leve.

Feasibility of external rhythmic cueing with the Google Glass for improving gait in people with Parkinson's disease.

New mobile technologies like smartglasses can deliver external cues that may improve gait in people with Parkinson's disease in their natural environment. However, the potential of these devices must first be assessed in controlled experiments. Therefore, we evaluated rhythmic visual and auditory cueing in a laboratory setting with a custom-made application for the Google Glass. Twelve participants (mean age = 66.8; mean disease duration = 13.6 years) were tested at end of dose. We compared several key gait parameters (walking speed, cadence, stride length, and stride length variability) and freezing of gait for three types of external cues (metronome, flashing light, and optic flow) and a control condition (no-cue). For all cueing conditions, the subjects completed several walking tasks of varying complexity. Seven inertial sensors attached to the feet, legs and pelvis captured motion data for gait analysis. Two experienced raters scored the presence and severity of freezing of gait using video recordings. User experience was evaluated through a semi-open interview. During cueing, a more stable gait pattern emerged, particularly on complicated walking courses; however, freezing of gait did not significantly decrease. The metronome was more effective than rhythmic visual cues and most preferred by the participants. Participants were overall positive about the usability of the Google Glass and willing to use it at home. Thus, smartglasses like the Google Glass could be used to provide personalized mobile cueing to support gait; however, in its current form, auditory cues seemed more effective than rhythmic visual cues.

Malignant teratoma in Klippel-Feil syndrome: a case report and review of the literature.

INTRODUCTION: Klippel-Feil syndrome is characterized by a congenital fusion of cervical vertebrae. Intracranial teratomas are nongerminomatous germ cell tumors and they account for 0.3 to 0.9% of all intracranial tumors. Teratomas with malignant transformation refer to lesions which give rise to malignant cancer of somatic type. The association between tumors of dermoid origin and Klippel-Feil malformation is extremely rare. Only 23 other cases have so far been reported, and only one case of dermoid tumor with areas of dedifferentiation on squamous cell carcinoma has been described. CASE PRESENTATION: We report the case of a 72-year-old white man with a 2-year history of gait and balance disturbances. A brain magnetic resonance imaging revealed a fourth ventricle neoplastic process with infiltrative features. He was operated through a suboccipital craniectomy with a C1 laminotomy and bilateral vertebral artery transposition. At 6-months follow-up, magnetic resonance imaging showed an early regrowth of the fourth ventricle tumor, with the same radiological features. CONCLUSIONS: Patients with Klippel-Feil malformation could develop posterior fossa dermoid tumors. The malignant potential of such tumors must be considered and surgery is recommended. Particular attention must be focused on the histopathological analysis in order to identify possible foci of malignant transformation.

Multiple spinal arteriovenous fistulas: A case-based review.

The occurrence of multiple spinal dural arteriovenous fistulas (AVFs) is rare. The majority of cases reported are synchronous and the lesions are mainly found at different spinal levels. Metachronous AVFs have been defined as lesions that manifest in a temporal sequence after treatment of a first AVF. In this report, we present two distinct cases of multiple spinal AVFs. Also, we review the main features of the cases previously reported, with emphasis on the proposed theories for the origin of multiple AVFs. In patients with failure to improve after treatment of a spinal DAVF, a whole-spine angiographic examination is mandatory, not only to ascertain the complete closure of the treated fistula, but also to look for a possible second lesion at a different spinal level.

Resistance to thyroid hormone caused by a mutation in thyroid hormone receptor (TR)α1 and TRα2: clinical, biochemical, and genetic analyses of three related patients.

BACKGROUND: The thyroid hormone receptor α gene (THRA) transcript is alternatively spliced to generate either thyroid hormone receptor (TR)α1 or a non-hormone-binding variant protein, TRα2, the function of which is unknown. Here, we describe the first patients identified with a mutation in THRA that affects both TRα1 and TRα2, and compare them with patients who have resistance to thyroid hormone owing to a mutation affecting only TRα1, to delineate the relative roles of TRα1 and TRα2. METHODS: We did clinical, biochemical, and genetic analyses of an index case and her two sons. We assessed physical and radiological features, thyroid function, physiological and biochemical markers of thyroid hormone action, and THRA sequence. FINDINGS: The patients presented in childhood with growth failure, developmental delay, and constipation, which improved after treatment with thyroxine, despite normal concentrations of circulating thyroid hormones. They had similar clinical (macrocephaly, broad faces, skin tags, motor dyspraxia, slow speech), biochemical (subnormal ratio of free thyroxine:free tri-iodothyronine [T3], low concentration of total reverse T3, high concentration of creatine kinase, mild anaemia), and radiological (thickened calvarium) features to patients with TRα1-mediated resistance to thyroid hormone, although our patients had a heterozygous mis-sense mutation (Ala263Val) in both TRα1 and TRα2 proteins. The Ala263Val mutant TRα1 inhibited the transcriptional function of normal receptor in a dominant-negative fashion. By contrast, function of Ala263Val mutant TRα2 matched its normal counterpart. In vitro, high concentrations of T3 restored transcriptional activity of Ala263Val mutant TRα1, and reversed the dominant-negative inhibition of its normal counterpart. High concentrations of T3 restored expression of thyroid hormone-responsive target genes in patient-derived blood cells. INTERPRETATION: TRα1 seems to be the principal functional product of the THRA gene. Thyroxine treatment alleviates hormone resistance in patients with mutations affecting this gene, possibly ameliorating the phenotype. These findings will help the diagnosis and treatment of other patients with resistance to thyroid hormone resulting from mutations in THRA. FUNDING: Wellcome Trust, NIHR Cambridge Biomedical Research Centre, Marie Curie Actions, Foundation for Development of Internal Medicine in Europe.

High beta activity in the subthalamic nucleus and freezing of gait in Parkinson's disease.

OBJECTIVE: Oscillatory activity in the beta band is increased in the subthalamic nucleus (STN) of Parkinson's disease (PD) patients. Rigidity and bradykinesia are associated with the low-beta component (13-20Hz) but the neurophysiological correlate of freezing of gait in PD has not been ascertained. METHODS: We evaluated the power and coherence of the low- and high-beta bands in the STN and cortex (EEG) of PD patients with (p-FOG) (n=14) or without freezing of gait (n-FOG) (n=8) in whom electrodes for chronic stimulation in the STN had been implanted for treatment with deep brain stimulation. RESULTS: p-FOG patients showed higher power in the high-beta band (F=11.6, p=0.002) that was significantly reduced after l-dopa administration along with suppression of FOG (F=4.6, p=0.042). High-beta cortico-STN coherence was maximal for midline cortical EEG electrodes, whereas the low-beta band was maximal for lateral electrodes (χ(2)=20.60, p<0.0001). CONCLUSIONS: The association between freezing of gait, high-beta STN oscillations and cortico-STN coherence suggests that this oscillatory activity might interfere in the frontal cortex-basal ganglia networks, thereby participating in the pathophysiology of FOG in PD.

Relationship between proprioception at the knee joint and gait ataxia in HSAN III.

BACKGROUND: Hereditary sensory and autonomic neuropathy type III features marked ataxic gait that progressively worsens over time. We assessed whether proprioceptive disturbances can explain the ataxia. METHODS: Proprioception at the knee joint was assessed using passive joint angle matching in 18 patients and 14 age-matched controls; 5 patients with cerebellar ataxia were also studied. Ataxia was quantified using the Brief Ataxia Rating Score, which ranged from 7 to 26 of 30. RESULTS: Neuropathy patients performed poorly in judging joint position: mean absolute error was 8.7° ± 1.0°, and the range was very wide (2.8°-18.1°); conversely, absolute error was only 2.7° ± 0.3° (1.6°-5.5°) in the controls and 3.0° ± 0.2° (2.1°-3.4°) in the cerebellar patients. This error was positively correlated to the degree of ataxia in the neuropathy patients but not the cerebellar patients. CONCLUSIONS: These results suggest that poor proprioceptive acuity at the knee joint is a major contributor to the ataxic gait associated with hereditary sensory and autonomic neuropathy type III.

Disability in atypical parkinsonian syndromes is more dependent on memory dysfunction than motor symptoms.

BACKGROUND: There is a gap in the systematic description and investigation of functional disability in corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP). Additionally, the relations between disability, apraxia, cognitive and behavioural changes are not well understood in atypical parkinsonian syndromes. METHODS: Fifty patients were included in this study (CBS = 18; PSP = 11), including a subgroup of primary progressive aphasia-nonfluent variant (PPA-nfv = 21) who were used as a control group given the clinic-pathological overlap. Functional disability (basic and instrumental activities of daily living), general cognition and behavioural changes were evaluated at baseline, with a subgroup of patients being reassessed after 16 months. RESULTS: The corticobasal syndrome group had the most marked disability in basic activities in comparison to progressive supranuclear palsy and primary progressive aphasia-nonfluent variant. Longitudinal decline was marked for all three groups. In a linear regression examining factors behind functional disability in CBS and PSP, memory dysfunction emerged as the main factor (48.5%), followed by apraxia (14.9%) and atypical parkinsonian symptoms (9.6%). CONCLUSIONS: Memory dysfunction is the most important factor in functional disability in CBS and PSP, which has to be taken into consideration in disease management, prognosis and planning of services to fully address patients' and families' needs.