Michela Rosso

Motor and Nonmotor Symptom Follow-Up in Parkinsonian Patients after Deep Brain Stimulation of the Subthalamic Nucleus

Objective: To evaluate motor and nonmotor symptoms in patients with Parkinson’s disease undergoing bilateral deep brain stimulation of the subthalamic nucleus (STN DBS). Methods: Thirty-six consecutive patients receiving bilateral STN stimulation implants were evaluated preoperatively as well as 12 and 24 months after surgery. Motor symptoms were assessed through the Unified Parkinson’s Disease Rating Scale (UPDRS). Data concerning nonmotor symptoms were collected from items of the UPDRS and 2 additional questions from clinical charts regarding constipation and urological dysfunction. Results: STN DBS was effective in controlling motor symptoms; concerning nonmotor symptoms, sleep quality and constipation improved after surgery as compared to baseline. Salivation, swallowing and sensory complaints were ameliorated to a comparable degree by the medication on state, whether preoperatively or postoperatively. With a lower dose of dopaminergic medication, however, the medication on state appeared to be a much larger percentage of the day postoperatively. No significant variations were detected in intellectual impairment, depression, thought disorders, motivation, falling unrelated to freezing, nausea, orthostatic hypotension and urological dysfunction. Conclusions: STN DBS effectively controls motor symptoms, while nonmotor features of advanced Parkinson’s disease patients are mostly unchanged after surgery, even though some specific aspects, notably sleep complaints and constipation, are ameliorated.

Deconstructing normal pressure hydrocephalus: Ventriculomegaly as early sign of neurodegeneration

Idiopathic normal pressure hydrocephalus (NPH) remains both oversuspected on clinical grounds and underconfirmed when based on immediate and sustained response to cerebrospinal fluid diversion. Poor long‐term postshunt benefits and findings of neurodegenerative pathology in most patients with adequate follow‐up suggest that hydrocephalic disorders appearing in late adulthood may often result from initially unapparent parenchymal abnormalities. We critically review the NPH literature, highlighting the near universal lack of blinding and controls, absence of specific clinical, imaging, or pathological features, and ongoing dependence for diagnostic confirmation on variable cutoffs of gait response to bedside fluid‐drainage testing. We also summarize our long‐term institutional experience, in which postshunt benefits in patients with initial diagnosis of idiopathic NPH persist in only 32% of patients at 36 months, with known revised diagnosis in over 25% (Alzheimers disease, dementia with Lewy bodies, and progressive supranuclear palsy). We postulate that previously reported NPH cases with “dual” pathology (ie, developing a “second” disorder) more likely represent ventriculomegalic presentations of selected neurodegenerative disorders in which benefits from shunting may be short‐lived, with a consequently unfavorable risk‐benefit ratio. Ann Neurol 2017;82:503–513

Antiparkinsonian therapy modifications in PD patients after STN DBS: A retrospective observational analysis

OBJECTIVE This study reports a retrospective analysis of 67 consecutive parkinsonian patients to assess changes in antiparkinsonian medications after Deep Brain Stimulation (DBS) of the Subthalamic Nucleus (STN). METHODS All antiparkinsonian drugs, including levodopa, dopamine agonists, associated drugs such as COMT and MAO inhibitors, amantadine and anticholinergics, were evaluated pre- and post-operatively at 1 and 3 years follow-up. RESULTS The levodopa mean daily dose was reduced approximately 60% after 1 year and remained stable after 3 years. Apomorphine, bromocriptine, tolcapone, entacapone and selegiline were withdrawn after STN DBS. Three years post-operatively, 9 patients (13.4%) no longer required levodopa and 6 patients (8.9%) completely stopped all dopaminergic medications. More patients were on monotherapy of either levodopa or dopamine agonist and fewer patients required a combined treatment of dopamine agonist and levodopa, compared to the pre-surgical condition. CONCLUSIONS STN DBS treated PD patients experience a significant long-term reduction and simplification of the pharmacological treatment.

Neuro-psychiatric therapy during chronic subthalamic stimulation in Parkinson's disease

BACKGROUND Neuro-psychiatric (NP) disturbances are highly prevalent in patients with Parkinsons disease (PD) and contribute to worsen quality of life. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is commonly utilized as surgical treatment for advanced PD with motor complications. The effectiveness of the procedure on motor symptoms is well established whereas the effects of STN-DBS on NP symptoms are less clear. The aim of our study was to analyze the postoperative pharmacological therapy for NP symptoms in a group of STN-DBS treated PD patients. Such therapy provides indirect information about the evolution of underlying NP disturbances during the follow-up in this group of PD patients. METHODS NP therapy (benzodiazepines, antidepressants, antipsychotics) was assessed in 48 consecutive PD patients treated by STN-DBS, preoperatively and postoperatively after 4 months, 1 year and 3 years. Motor symptoms were evaluated by the Unified PD Rating Scale (UPDRS) and levodopa equivalence daily dose (LEDD) was calculated. Cognitive, mood and anxiety assessments were performed with appropriate rating scales. RESULTS The number of patients treated with antidepressant drugs gradually increased during the follow-up. The use of antipsychotic drugs was stable until 1 year, with a subsequent increase at 3 years. Benzodiazepines were given to fewer patients immediately after surgery. CONCLUSIONS Pharmacological treatment supplies further information about NP symptoms in the follow-up of PD patients undergoing STN stimulation.

Autonomic dysfunction in Parkinson's disease: A prospective cohort study: Prospective PD Autonomic Function Assessment

Background: Dysautonomia is a frequent and disabling complication of PD, with an estimated prevalence of 30‐40% and a significant impact on the quality of life.

Prevalence and burden of dysautonomia in advanced Parkinson's disease

We sought to examine the prevalence and burden of dysautonomia in patients with advanced Parkinson’s disease (PD) treated with subthalamic deep brain stimulation (STNDBS) and levodopa-carbidopa intestinal gel infusion (LCIG). Using a standardized battery of autonomic tests, blood pressure measurement protocol, and the Scale for Outcomes in Parkinson’s Disease-Autonomic (SCOPA-AUT), 60 consecutive PD patients treated with STN-DBS (n 5 30) and LCIG (n 5 30) were classified according to the presence or absence of dysautonomia. We evaluated the impairment in activities of daily living/instrumental activities of daily living (ADL/iADL), adjusting for cognitive impairment, as measured by the Montreal Cognitive Assessment (MoCA), age, and motor severity using the motor subscale of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS-III). Additional measures included SCOPA-AUT, Orthostatic Hypotension Symptom Assessment, and the PD Quality-of-Life Questionnaire (PDQ-8). Binary logistic regression was used to estimate the impact (odds ratio [OR]) of dysautonomia on ADL/iADL, adjusting for cognitive impairment, age, and motor severity. A multiple linear regression model was used to estimate the correlation between SCOPA-AUT and PDQ-8. In addition, analysis of covariance was used to estimate the extent to which the dependent variables, ADL/iADL, adjusted for MoCA, age, and MDS-UPDRS-III, were influenced by (1) symptomatic state (symptomatic vs asymptomatic orthostatic hypotension); and (2) therapy (STN-DBS vs LCIG). Mann-Whitney and Fisher’s tests were used for comparisons between groups. The overall prevalence of dysautonomia in this unselected population was 48.3% (29 of 60 patients), similar to that in the STN-DBS (50%) and LCIG (46.7%) cohorts (P 5 0.796). Adjusted analysis showed that dysautonomia was independently associated with a threefold impairment in ADL/iADL (OR, 2.850; 95% CI, 1.044-10.326; P 5 0.042). There was a robust correlation between autonomic symptoms (SCOPA-AUT) and quality-of-life impairment (P< 0.001). The strongest correlation was for gastrointestinal (P< 0.001), urinary/sexual (P 5 0.01), and cardiovascular (P 5 0.017) domains. Adjusted ADL/iADL scores differed between patients with and without orthostatic hypotension (P 0.047). In post hoc analyses, symptomatic (15.0%) and asymptomatic (11.7%) orthostatic hypotension worsened ADL/iADL to a similar extent (P 0.045) compared with patients without orthostatic hypotension (Fig. 1). The adjusted ADL/iADL scores was similar in the STN-DBS and LCIG cohorts (P 0.473). Subanalysis of autonomic domains (Fig. 1) revealed worse cardiovascular impairment in the LCIG cohort (P 5 0.039), potentially because of higher dopaminergic dosage (Supplementary Table) and worse pupillomotor impairment in the STN-DBS cohort (P 5 0.026), plausibly associated with electrical spread to the optic tract.

Subcutaneous vs. intravenous immunoglobulin in CIDP: pharmacokinetic and clinical response

Dear Editor, Subcutaneous immunoglobulin (SCIg) represents an innovative and effective alternative to intravenous immunoglobulin (IVIg) for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) (Cocito et al., 2014; 2015). Different tolerability profiles have been reported between SCIg and IVIg, with the SCIg possible advantages of fewer side effects and greater independence from hospital care (Markvardsen et al., 2013; Rajabally, 2014). However, the two routes of administration are associated with a distinctive pharmacological profile (Eftimov et al., 2009), which may result in a differential clinical efficacy. We compare the pharmacokinetic data of eight CIDP patients shifted from IVIg monthly infusions to SCIg weekly administrations, evaluating the possible correlations between clinical response and IgG plasma levels. All patients were receiving IVIg for at least 6 months, reporting a “wear-off effect” between each infusion (increase of≥ 1 point at the inflammatory neuropathy cause and treatment [INCAT] score and/or decrease of≥1 point at the medical research council [MRC] scale). IVIg monthly dose (average dose: 1.25± 0.38 g/ kg/month; ranging from 1 to 2 g/kg/month, according to the individual clinical response) was converted to an equivalent dose of SCIg (20% solution of immunoglobulin ready-to-use) delivered via a programmable pump at the patient’s domicile. The shift from IVIg to SCIg was due to fluctuations in clinical response (wear-off) and patient’s desire of greater independence from hospital care (IVIg administration at the patient’s domicile is not allowed in Italy). Blood samples (5 ml), clinical scales (INCAT and MRC) and Martin vigorimeter measurements were collected immediately before the first day (T-1) and after the second day (T0) of the last IVIg cycle, and at the following time-points: (1) before the first SCIg administration (2 weeks after the last IVIg

CIDP-like neuropathies in graft versus host disease.

Cases of chronic inflammatory demyelinating poliradiculoneuropathy (CIDP) have been reported in hematopoietic stem cells transplantation complicated by graft versus host disease (GVHD). A systematic review of the CIDP‐like neuropathies associated with GVHD was conducted until January 2015, analyzing the clinical presentation and the response to different therapeutic regimens. Nineteen patients have been reported in literature including the present one. Fourteen subjects fulfilled the criteria for CIDP, whereas two cases presented with an asymmetric motor onset and one showed motor involvement only associated with anti‐ganglioside antibodies. In addition, two subjects already affected by CIDP developed a significant relapse after GVHD. This study reviews the literature data and reports one additional case of CIDP and GVHD, suggesting that the two clinical entities might share a similar immunological background.

Peripheral Nerve Ultrasonography in Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Multifocal Motor Neuropathy: Correlations with Clinical and Neurophysiological Data

Objective. This cross-sectional study analyzes the pattern of ultrasound peripheral nerve alterations in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) at different stages of functional disability. Material and Methods. 22 CIDP and 10 MMN patients and a group of 70 healthy controls were evaluated with an ultrasound scan of the median, ulnar, peroneal, tibial, and sural nerves. Results were correlated with clinical disability scales and nerve conduction studies. Results. Patients with intermediate functional impairment showed relatively larger cross-sectional areas than subjects with either a milder (p < 0.05) or more severe impairment (p < 0.05), both in CIDP and in MMN. In addition, MMN was associated with greater side-to-side intranerve variability (p < 0.05), while higher cross-sectional areas were observed in CIDP (p < 0.05) and in nerve segments with predominantly demyelinating features (p < 0.05). Higher CSA values were observed in nerves with demyelinating features versus axonal damage (p < 0.05 for CIDP; p < 0.05 for MMN). Discussion and Conclusions. Greater extent of quantitative and qualitative US alterations was observed in patients at intermediate versus higher functional disability and in nerves with demyelinating versus axonal damage. CIDP and MMN showed differential US aspects, with greater side-to-side intranerve variability in MMN and higher cross-sectional areas in CIDP.

Pure Autonomic Failure Versus Prodromal Dysautonomia in Parkinson's Disease: Insights from the Bedside

Autonomic failure may include orthostatic hypotension, supine hypertension, bowel and bladder disturbances, impaired thermal regulation, and sexual dysfunction, all of which can be features of Parkinsons disease (PD) and other a‐synucleinopathies. All patients with pure autonomic failure, most patients with multiple system atrophy, and 18% of patients with PD will develop symptomatic orthostatic hypotension. However, the extent of central and peripheral norepinephrine deficiency, parasympathetic nuclei degeneration, and arterial baroreflex failure may be differentially impaired in these disorders. Consequently, clinical features and prognostic implications of autonomic dysfunction in a‐synucleinopathies may be more complex than previously envisioned. The case described in this report highlights the clinical similarities between PD and pure autonomic failure, raising the question of whether pure autonomic failure represents a restricted Lewy body synucleinopathy or an early manifestation of PD.