Alessia Tavella

Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: comparison of pre- and postoperative neuropsychological evaluation

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for the motor symptoms of advanced Parkinsons disease (PD). The aim of this study was to assess the effect of the bilateral surgical procedure and STN DBS on the neuropsychological functions. Twenty Parkinsons disease patients underwent a neuropsychological assessment before and 6 months after surgery in four different conditions: medication on (with levodopa) and medication off (without levodopa) during the preoperative period, medication on/stimulation on (levodopa plus stimulators switched on) and medication off/stimulation on (stimulators switched on without levodopa) during the postoperative period. We did not find any significant difference in the four conditions for all the neuropsychological tests, confirming the lack of an overall cognitive decline after surgery. From a neuropsychological point of view, these results seem to indicate that bilateral STN DBS is a safe treatment for advanced PD.

Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: long-term follow-up.

Abstract. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown to be an effective therapy for the treatment of advanced Parkinsons disease (PD). Fortyseven patients were bilaterally implanted for STN DBS and clinically evaluated according to the Core Assessment Program for Intracerebral Transplantations before surgery and 3, 12 and 24 months after surgery. Electrical stimulation led to a significant improvement in motor symptoms and in the quality of life, allowing a significant reduction of dopaminergic drugs with a consequent improvement of drug-induced dyskinesias. Statistical differences were observed between UPDRS parts II, III and IV values and daily levodopa dosage in the pre- and postoperative periods, while no differences were evident between the 3 postoperative conditions.

Deep brain stimulation of subthalamic nucleus: behavioural modifications and familiar relations

Abstract The present study investigated behavioural modifications and familiar relations in a group of 15 parkinsonian patients treated with bilateral deep brain stimulation of the subthalamic nucleus. In 70% of the patients, during the first months after surgery we observed a euphoric mood owing to motor sugins amelioration, but a series of problems (fear to come back to the pre-operative condition, sense of failure, slowness in changing the old habits) arose when it was necessary to adjust the parameters of stimulation and the pharmacological therapy to obtain a stable clinical picture. The caregivers showed an aggressive behaviour as reaction to the persistent psychological dependence of the patients. This distressed condition could be the cause of the onset of incomprehensions within the couple.

Electrophysiological findings of peripheral neuropathy in newly diagnosed type II diabetes mellitus.

Abstract  This study was aimed at assessing the electrophysiological signs of peripheral neuropathy in diabetes mellitus (DM) type II patients at diagnosis. Nerve conduction studies (NCS) of median, ulnar, peroneal, tibial and sural nerves were performed in 39 newly diagnosed DM subjects and compared to those of 40 healthy controls. Metabolic indices were also investigated. Electrophysiological alterations were found in 32 (82%) of the DM patients, and more than half of them (62.2%) showed multiple (two to five) abnormal parameters. Because most of the subjects (84.4%) had from two to five nerves involved, these alterations were widespread in the seven nerves evaluated. Forty‐two percent of the patients had NCS alterations suggestive of distal median mononeuropathy, implying that metabolic factors in DM make the median nerve more susceptible to focal entrapment. A reduced sensory nerve action potential (SNAP) amplitude was observed in the median nerve in 70% of the patients, in the ulnar in 69% and in the sural nerve only in 22%. In the presence of a decrease in the SNAP amplitude of the ulnar or median nerve, the SNAP amplitude of the sural nerve was normal in 82 or 80% of the subjects, respectively. This finding may be in keeping with a distal involvement of the sensory fibres, as explored by routine median or ulnar NCS. No correlation was found between metabolic indices and NCS parameters. In conclusion, a high percentage of newly diagnosed DM patients show signs of neuropathy, and upper limb nerve sensory NCS seem to be more sensitive in detecting it than lower limb NCS.

Temporal changes in movement time during the switch of the stimulators in Parkinson's disease patients treated by subthalamic nucleus stimulation.

Objective: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a very effective therapy for the advanced phase of Parkinson’s disease (PD). The functional inhibition of this nucleus is responsible for a significant improvement of cardinal motor symptoms of PD. The aim of the study was the assessment of the effectiveness of STN DBS on bradykinesia by the analysis of movement time (MT) in 2 conditions: with the stimulators turned on (‘stim-on’) or off (‘stim-off’). Methods: After pharmacological wash-out, 10 patients submitted to bilateral STN DBS were studied with an MT analyser in 3 phases: stim-on, stim-off and stim-on again, in order to establish the time course of MT lengthening, the posteffect duration and the latency of the effect of STN DBS. MT data were then compared with the UPDRS motor scores. Results: After turning off the stimulators, MT progressively increases, reaching a plateau after about 30 min, which then lasts for the subsequent observation time (2 h). A significant elongation is achieved after the first 5 min. Upon pulse generator activation, MT shows a dramatic shortening, already significant after 2 min. Moreover, we observed a significant correlation between MT and the severity of PD, higher with bradykinesia than with rigidity or tremor. Conclusion: Our findings show a relevant effect of STN DBS on MT, a parameter strongly related to bradykinesia. This study confirms the effectiveness of STN inhibition on the whole parkinsonian triad, suggesting that this target can be considered a proper choice for the surgical treatment of advanced PD.

Multifocal motor neuropathy during treatment with infliximab

Dear Editor, Infliximab (Remicade ) is a chimeric human/murine immunoglobulin G1 (IgG1) anti-tumour necrosis factor-a (TNF) antibody. Although TNF antagonists are among the most potent and rapidly effective treatments for rheumatoid arthritis (RA) (Olsen and Stein, 2004), a number of adverse effects, including induction or worsening of demyelinating central nervous system diseases, have been reported (Mohan et al., 2001; Sicotte and Voskuhl, 2001). Three cases of motor neuropathy with conduction blocks (Singer et al., 2004; Rodriguez-Escalera et al., 2005) have been reported in patients on infliximab; two of these patients had Crohn’s disease and seronegative arthritis, while one had polyarthritis and Hepatitis C with mixed cryoglobulinaemia. Herein, we report yet another patient with onset of multifocal motor neuropathy (MMN) and conduction blocks during infliximab treatment. A 40-year-old woman with a 10-year history of RA was started on infliximab treatment in January 2003 (3 mg/kg intravenous every 8 weeks) with a satisfactory response in the months that followed. However, she developed asymmetric progressive weakness of right forearm flexion and of intrinsic muscles of right hand in October 2003. Neurological evaluation (January 2004) disclosed the presence of severe weakness of the right biceps brachii (0/5 according to Medical Research Scale Score), the right extensor carpi radialis, extensor digitorum communis, extensor indicis, abductor pollicis brevis, abductor digiti minimi, and interossei (3/5) and moderate weakness of the left deltoid, extensor digitorum communis, extensor index, interossei, left tibialis anterior, and gastrocnemius (4/5). Tendon reflexes were normal apart from the absence of response in the right biceps. There was no detectable sensory loss. The neurological examination was otherwise unremarkable. Nerve conduction studies showed the presence of definite conduction block in both median and ulnar nerves, right radial, left peroneus, and tibial nerves. A significant decrease in motor conduction velocity was evident in both the median nerves. Sensory conduction studies of the bilateral median, radial, ulnar and sural nerves were unremarkable. Brain and spinal cord magnetic resonance imaging and cerebrospinal fluid examination were normal. DNA analysis was negative for the presence of the 1.5-Mb deletion in chromosome 17p11.2 associated with hereditary neuropathy with liability to pressure palsy. Routine screening tests for thyroid pathologies, hepatitis, cryoglobulinaemia and vasculitis were negative. IgM anti-GM1 antibodies were positive at high titre (1 : 640) (Antigen Coated Membrane Strips Euroimmun). The patient satisfied the diagnostic criteria for MMN established by Olney (Olney et al., 2003). Infliximab treatment was stopped in March 2004, and the patient was treated with intravenous immunoglobulins (1 g/kg/day for 2 days monthly), and muscle strength progressively improved. At the last follow up, in February 2005, there was a marked increase in the muscle strength, with only residual moderate weakness (4/5) affecting only the biceps, extensors carpi radialis and interossei muscles. Nerve conduction studies demonstrated a reduction in the number of blocks. The timing of the onset of neuropathy reported in literature varies greatly, i.e., after 2 years of infliximab therapy in one case, 3 months in another (Singer et al., 2004), 14 weeks in a case reported by RodriguezEscalera et al. (2005) and after 9 months in our case. The therapeutic schedule also varied in all cases. A spontaneous remission of the neuropathy was observed in the two cases reported by Singer, after suspension of the treatment. Whilst in our case and that of RodriguezEscalera, a therapy with immunoglobulins was administered in both cases with a positive outcome. Lastly, in both our cases and the case reported by RodriguezEscalera, there was a positivity to antiganglioside antibodies. MMN was not a neurologic complication of RA (Nobile-Orazio et al., 2005), and the onset of MMN Address correspondence to: Dr. Dario Cocito, MD, U.O. Neurofisiologia Clinica, Dipartimento di Neuroscienze, Università di Torino, Via Cherasco 15, 10126 Torino, Italy, Tel: þ39-0116-335243; Fax: þ39-0116-963487; E-mail: dariococito@yahoo.it Journal of the Peripheral Nervous System 10:386–387 (2005)

Deep brain stimulation of the subthalamic nucleus in PD: an analysis of the exclusion causes.

OBJECTIVE Deep Brain Stimulation (DBS) of the Subthalamic Nucleus (STN) represents a proper choice for the treatment of advanced Parkinsons disease (PD). A correct selection of the patients as candidates for the surgery is essential for a good outcome. In this study, we analyzed the exclusion causes of a series of PD patients hospitalized for the selection protocol. METHODS Ninety-eight PD patients as potential candidates for the STN DBS were studied. All patients were hospitalized and underwent a clinical evaluation of the PD stage, a levodopa challenge, a MR of the brain and a neuropsychological assessment. RESULTS The percentage of subjects considered not suitable for the surgery was 29.6%. A single cause of exclusion was present in 65.5% of not suitable patients, while multiple causes were present in 34.5%. The most frequent cause of exclusion was the finding of neuropsychological or psychic disorders (48.3%); in 37.9% of the patients, the motor disability was not severe enough to justify the surgery, while in 31%, we found relevant abnormalities at the brain MR. Three patients (10.3%) were poorly motivated for the surgery, while in three others (10.3%), we found a significant illness other than PD. CONCLUSIONS The finding that about 30% of the PD patients potentially suitable for STN DBS presents some exclusion causes underlines the importance of a careful selection of the candidates for this surgery.

Deep brain stimulation of the subthalamic nucleus: selection of patients and clinical results

Abstract Deep brain stimulation of the subthalamic nucleus has been proved to be an effective treatment for advanced Parkinsons disease when therapeutical strategies have failed. A correct selection of candidates for surgery is fundamental to obtain a good clinical effect. In this study we present our protocol of patient selection. In addition we report the data relative to the different causes of exclusion and the clinical efficacy of the electrical stimulation of the subthalamic nucleus at 3 months and 1 year follow-up.

Pain affects the quality of life of neuropathic patients

The aim of this study was to verify the extent to which the presence of pain affects the quality of life (QoL) of neuropathic patients. The patients were selected in our Department of Peripheral Nervous System Diseases. We enrolled 120 consecutive patients with chronic polyneuropathy who had not received continuous pain therapy during the two months preceding study entry, and administered them the Total Neuropathy Score (TNS), the official Italian version of the SF-36 and the Italian Pain Questionnaire (QUID). Our main finding was that the QoL is affected not only by the presence of neuropathy, but also by the presence and intensity of pain: the physical aspect of the QoL correlated only weakly with the TNS, but pain was closely related to a worsening in this parameter; moreover, the mental domains of the SF-36 were only correlated with pain. Pain per se worsens the QoL of neuropathic patients, regardless of disease severity.

A further critical evaluation of requests for electrodiagnostic examinations.

The aim of this study was to evaluate the impact of electrophysiological (EDX) tests in the clinical management and diagnosis of patients, and the appropriateness of the referral diagnosis. A study was carried out in three electrodiagnostic services in the Torino area, over a 12-month period. In our study 3,900 individuals (2,340 females, 1,560 males) were evaluated. Patients underwent EDX examinations including nerve conduction study, electromyography and repetitive stimulation test. Most patients had been sent for EDX tests by specialists. Specialists suspected mainly polyneuropathy, whilst general practitioners suspected mainly carpal tunnel syndrome. Seventy-two percent of the requests were correctly formulated, 55% by general practitioners and 77% by specialists. There was a concordance between the results of the EDX tests and diagnostic hypothesis 40% of the time. This study confirms the usefulness and diagnostic impact of EDX examinations and evidences the amount of time and resources wasted as a result of incorrect or incomplete requests.