Collective physician perspectives on non-oral medication approaches for the management of clinically relevant unresolved issues in Parkinson's disease: Consensus from an international survey and discussion program

Navigate PD was an educational program established to supplement existing guidelines and provide recommendations on the management of Parkinson's disease (PD) refractory to oral/transdermal therapies. It involved 103 experts from 13 countries overseen by an International Steering Committee (ISC) of 13 movement disorder specialists. The ISC identified 71 clinical questions important for device-aided management of PD. Fifty-six experts responded to a web-based survey, rating 15 questions as ‘critically important;’ these were refined to 10 questions by the ISC to be addressed through available evidence and expert opinion. Draft guidance was presented at international/national meetings and revised based on feedback. Key take-home points are: • Patients requiring levodopa >5 times daily who have severe, troublesome ‘off’ periods (>1–2 h/day) despite optimal oral/transdermal levodopa or non-levodopa-based therapies should be referred for specialist assessment even if disease duration is <4 years. • Cognitive decline related to non-motor fluctuations is an indication for device-aided therapies. If cognitive impairment is mild, use deep brain stimulation (DBS) with caution. For patients who have cognitive impairment or dementia, intrajejunal levodopa infusion is considered as both therapeutic and palliative in some countries. Falls are linked to cognitive decline and are likely to become more frequent with device-aided therapies. • Insufficient control of motor complications (or drug-resistant tremor in the case of DBS) are indications for device-aided therapies. Levodopa-carbidopa intestinal gel infusions or subcutaneous apomorphine pump may be considered for patients aged >70 years who have mild or moderate cognitive impairment, severe depression or other contraindications to DBS

Altered Cerebellar-Cerebral Functional Connectivity in Geriatric Depression

Although volumetric and activation changes in the cerebellum have frequently been reported in studies on major depression, its role in the neural mechanism of depression remains unclear. To understand how the cerebellum may relate to affective and cognitive dysfunction in depression, we investigated the resting-state functional connectivity between cerebellar regions and the cerebral cortex in samples of patients with geriatric depression (n = 11) and healthy controls (n = 18). Seed-based connectivity analyses were conducted using seeds from cerebellum regions previously identified as being involved in the executive, default-mode, affective-limbic, and motor networks. The results revealed that, compared with controls, individuals with depression show reduced functional connectivity between several cerebellum seed regions, specifically those in the executive and affective-limbic networks with the ventromedial prefrontal cortex (vmPFC) and increased functional connectivity between the motor-related cerebellum seed regions with the putamen and motor cortex. We further investigated whether the altered functional connectivity in depressed patients was associated with cognitive function and severity of depression. A positive correlation was found between the Crus II–vmPFC connectivity and performance on the Hopkins Verbal Learning Test-Revised delayed memory recall. Additionally, the vermis–posterior cinglate cortex (PCC) connectivity was positively correlated with depression severity. Our results suggest that cerebellum–vmPFC coupling may be related to cognitive function whereas cerebellum–PCC coupling may be related to emotion processing in geriatric depression

Behavioural Significance of Cerebellar Modules

A key organisational feature of the cerebellum is its division into a series of cerebellar modules. Each module is defined by its climbing input originating from a well-defined region of the inferior olive, which targets one or more longitudinal zones of Purkinje cells within the cerebellar cortex. In turn, Purkinje cells within each zone project to specific regions of the cerebellar and vestibular nuclei. While much is known about the neuronal wiring of individual cerebellar modules, their behavioural significance remains poorly understood. Here, we briefly review some recent data on the functional role of three different cerebellar modules: the vermal A module, the paravermal C2 module and the lateral D2 module. The available evidence suggests that these modules have some differences in function: the A module is concerned with balance and the postural base for voluntary movements, the C2 module is concerned more with limb control and the D2 module is involved in predicting target motion in visually guided movements. However, these are not likely to be the only functions of these modules and the A and C2 modules are also both concerned with eye and head movements, suggesting that individual cerebellar modules do not necessarily have distinct functions in motor control

Pregnancy-related pelvic girdle pain: an update

A large number of scientists from a wide range of medical and surgical disciplines have reported on the existence and characteristics of the clinical syndrome of pelvic girdle pain during or after pregnancy. This syndrome refers to a musculoskeletal type of persistent pain localised at the anterior and/or posterior aspect of the pelvic ring. The pain may radiate across the hip joint and the thigh bones. The symptoms may begin either during the first trimester of pregnancy, at labour or even during the postpartum period. The physiological processes characterising this clinical entity remain obscure. In this review, the definition and epidemiology, as well as a proposed diagnostic algorithm and treatment options, are presented. Ongoing research is desirable to establish clear management strategies that are based on the pathophysiologic mechanisms responsible for the escalation of the syndrome's symptoms to a fraction of the population of pregnant women

Algorithms for the treatment of motor problems in Parkinson's disease

Several different strategies are effective for medical treatment of motor problems in Parkinson's disease (PD). Many guidelines and evidence-based reviews are available, but there is no documentation or consensus in favor of just one treatment strategy. This review presents two algorithms that may be helpful when deciding how to treat a PD patient at various stages of the disease. The first algorithm suggests one way to treat PD from the first onset of motor symptoms. It is largely based on treatment recommendations from the Scandinavian countries and Germany. The other algorithm is meant as assistance for choosing among the different device-aided treatments for advanced PD. There is not sufficient comparative data to recommend one particular line of treatment, neither in early PD nor in advanced disease with motor complications. Individualized treatment is needed for each patient. The current algorithms only represent an alternative for aiding treatment decisions

Hypothalamocerebellar and cerebellohypothalamic projections - circuits for regulating nonsomatic cerebellar activity.

Cerebellar involvement in visceral and affective responses is known from physiological and behavioral studies, but the pathways involved in these responses have remained enigmatic. Over the last ten years neuroanatomical studies have shown that the cerebellum and hypothalamus are interconnected by direct hypothalamocerebellar and cerebellohypothalamic projections and by a multitude of indirect pathways. The hypothalamocerebellar projection terminates in the cerebellar nuclei and in all layers of the cerebellar cortex as multilayered fibres. This projection is, at least in part, histaminergic. New immunocytochemical experiments indicate that small numbers of hypothalamocerebellar neurones may contain GABA- or glycine-like immunoreactivity. GABA may function as a transmitter in hypothalamocerebellar fibres, probably in conjunction with histamine, but it is not clear whether glycine may also function as a transmitter or only serve metabolic functions. The bidirectional pathways between the cerebellum and hypothalamus may be part of the circuits through which the cerebellum participates in the modulation of a variety of nonsomatic events. In addition, new observations on patients with well localized cerebellar lesions reveal simultaneous somatic and visceral dysfunction. Recent research on direct hypothalamocerebellar pathways and on other connections between hypothalamus and cerebellum is reviewed. It is hypothesized that the cerebellum may act as a general modulator and coordinator of a wide range of central nervous activities, somatic as well as nonsomatic