Arrigo Moglia

Relationship between hallucinations, delusions, and rapid eye movement sleep behavior disorder in Parkinson's disease.

Psychotic symptoms are the main and the most disabling “nonmotor” complications of Parkinsons disease (PD), the pathophysiology of which is poorly recognized. Polysomnographic studies have shown a relationship between visual hallucinations and rapid eye movement (REM) sleep. The objective of this study is to clarify the relationship between psychotic symptoms and REM sleep behavior disorder (RBD) in PD. In a Parkinsons disease outpatient unit, 289 consecutive subjects with idiopathic PD were administered (in the period from January to December 2002) a multiple‐choice questionnaire and structured interview on sleep and mental disorders. RBD was diagnosed in accordance with the minimal diagnostic criteria of the International Classification of Sleep Disorders. Hallucinations and delusional disorders were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders‐IV criteria. The presence or absence of psychotic symptoms, of RBD, and of daytime sleepiness, as well as motor status, cognitive status, and mood were assessed. Approximately 32% (n = 92) of the subjects presented with psychotic disorders; 30% (n = 86) had experienced hallucinations; 2% (n = 6) had delusions without hallucinations. Sixty‐two (72%) hallucinators reported nocturnal hallucinations. A total of 6.6% (n = 19) of the subjects complained of a delusional disorder. There were 26.6% (n = 77) of subjects who presented with RBD: 28 (36%) with onset before and 49 (63%) with onset after PD diagnosis. The presence of RBD was associated with an increased risk of manifesting hallucinations and delusions (odds ratio [OR], 2.73). Other independent clinical factors found to have an effect on psychotic disorders were cognitive impairment (OR, 3.92), disease duration (OR, 2.46), advanced age (OR, 2.34), and severity of motor symptoms (OR, 2.06). These results suggest that RBD is widely associated with psychosis in PD.

A randomised, double-blind, dose-ranging study to evaluate efficacy and safety of three doses of botulinum toxin type A (Botox) for the treatment of spastic foot

Botulinum toxin A (BTX) injections have been used successfully in the treatment of post-stroke foot spasticity, but the optimal dose-response relationship for selected muscles has yet to be established. The aim of this study was to outline beneficial and unwanted effects of three different doses of BTX in the treatment of spastic foot. In this randomised, double-blind, dose-ranging study, 45 spastic feet were randomly allocated to one of three groups, each of which was treated with a different dosage of BTX. The doses were decided on the basis of suggestions in the literature. Outcome measures (Modified Ashworth Scale, Medical Research Council Scale, gait assessment, presence of Achilles tendon clonus, Visual Analogue Scales for Gait Function and Pain, Adverse Effects scale) were applied at baseline, 4 weeks and 4 months after treatment. All the groups showed significant scales scores improvements after treatment with BTX. Group II (mean BTX total dose: 322 U) and Group III (mean BTX total dose: 540 U) showed a greater and more prolonged response than Group I (mean BTX total dose: 167 U). Group III showed the highest rate of adverse effects 4 weeks post-treatment. BTX injections constitute a useful and safe method of improving post-stroke foot spasticity, associated pain, gait speed and function. In particular, the medium BTX dosages (320 UI spread over 2–5 muscles) were found to be both safe and effective in producing long-lasting improvement of spastic foot dysfunction.

Surface mechanomyogram reflects the changes in the mechanical properties of muscle at fatigue

Abstract The contractile properties of muscle are usually investigated by analysing the force signal recorded during electrically elicited contractions. The electrically stimulated muscle shows surface oscillations that can be detected by an accelerometer; the acceleration signal is termed the surface mechanomyogram (MMG). In the study described here we compared, in the human tibialis anterior muscle, changes in the MMG and force signal characteristics before, and immediately after fatigue, as well as during 6 min of recovery, when changes in the contractile properties of muscle occur. Fatigue was induced by sustained electrical stimulation. The final aim was to evaluate the reliability of the MMG as a tool to follow the changes in the mechanical properties of muscle caused by fatigue. Because of fatigue, the parameters of the force peak, the peak rate of force production and the peak of the acceleration of force production (d2F/dt2) decreased, while the contraction time and the half-relaxation time (½-RT) increased. The MMG peak-to-peak (p-p) also decreased. The attenuation rate of the force oscillation amplitude and MMG p-p at increasing stimulation frequency was greater after fatigue. With the exception of ½-RT, all of the force and MMG parameters were restored within 2 min of recovery. A high correlation was found between MMG and d2F/dt2 in un-fatigued muscle and during recovery. In conclusion, the MMG reflects specific aspects of muscle mechanics and can be used to follow the changes in the contractile properties of muscle caused by localised muscle fatigue.

Immune-mediated neuropathies in myeloma patients treated with bortezomib.

OBJECTIVE Bortezomib is a new chemotherapeutic drug available for the treatment of lymphoid disorders, including multiple myeloma. Although its primary mechanism of action is proteasome inhibition, other mechanisms can contribute to the therapeutic effects, including modulation of inflammatory cytokines and immune response. One of the main toxic effects of bortezomib is peripheral neuropathy, usually occurring in the form of a painful, sensory axonal neuropathy. The mechanisms of peripheral damage, however, are still unclear. We here report a series of patients treated with bortezomib, who developed a peripheral damage possibly related to immuno-mediated, rather than toxic, mechanisms. METHODS Five patients who developed a peripheral neuropathy with severe motor involvement under bortezomib treatment underwent CSF, electrophysiological, and spinal cord MRI examinations. RESULTS Peripheral damage was characterized by: demyelinating or mixed axonal-demyelinating neuropathy, with prominent motor involvement; albumin-cytological dissociation; lumbar root enhancement on MRI in 2/5 patients; favourable outcome in 4/5 patients after immune treatments, either steroids (2 patients) or IVIg (2 patients). CONCLUSIONS In some instances, the peripheral damage associated with bortezomib may recognize immuno-mediated mechanisms. SIGNIFICANCE This form of bortezomib-associated neuropathy needs to be recognized as treatable condition, as it may respond to immune therapies. Unexplained worsening of neurological dysfunction despite bortezomib discontinuation, with prominent motor involvement and CSF signs of inflammation, may be the clues to this complication.

Electrophysiologic patterns of oral-pharyngeal swallowing in parkinsonian syndromes

Objectives: To assess the presence, severity, and differences in dysphagia in Parkinson disease (PD), Parkinson variant of multiple system atrophy (MSA-P), and progressive supranuclear palsy (PSP), and to study the pathophysiology of swallowing abnormalities in these disorders. Methods: We applied an electrophysiologic method to evaluate oral-pharyngeal swallowing. We analyzed the following measures: duration of EMG activity of suprahyoid/submental muscles (SHEMG-D); duration of laryngeal–pharyngeal mechanogram (LPM-D); duration of the inhibition of the cricopharyngeal muscle activity (CPEMG-ID); interval between onset of EMG activity of suprahyoid/submental muscles and onset of laryngeal-pharyngeal mechanogram (I-SHEMG-LPM); and swallowing reaction time (SRT). Results: The prolongation of I-SHEMG-LPM was more typical in PD, whereas the most distinctive finding both in patients with PSP and MSA-P was the reduction or the absence of CPEMG-ID early in the course of the disease. Conclusions: Involvement of the peduncolo-pontine tegmental nucleus, with subsequent dysfunction of basal ganglia and of the medullary central pattern generator of swallowing, may account for the abnormalities detected in these parkinsonian syndromes. The method described was able to identify swallowing abnormalities also in patients without symptoms of dysphagia and to evaluate dysphagia severity in all patients.

Effects of hypnosis on diffuse noxious inhibitory controls

The neurophysiological mechanisms of hypnotic analgesia are still under debate. It is known that pain occurring in one part of the body (counterstimulation) decreases pain in the rest of the body by activating the diffuse noxious inhibitory controls (DNICs). The aim of this study was to explore the effects of hypnosis on both pain perception and heterotopic nociceptive stimulation. The A forms of both the Harward Group Scale of Hypnotic Susceptibility and the Stanford Hypnotic Susceptibility Scale were administered to 50 healthy students. Twenty subjects were selected and assigned to two groups: group A, consisting of 10 subjects with high hypnotic susceptibility; and group B, consisting of 10 subjects with low hypnotic susceptibility. The subjects were then randomly assigned first to either a control session or a session of hypnotic analgesia. The nociceptive flexion reflex (RIII) was recorded from the biceps femoris muscle in response to stimulation of the sural nerve. The subjective pain threshold, the RIII reflex threshold, and the mean area with suprathreshold stimulation were determined. Heterotopic nociceptive stimulation was investigated by the cold-pressor test (CPT). During and immediately after the CPT, the subjective pain threshold, pain tolerance, and mean RIII area were determined again. The same examinations were repeated during hypnosis. Hypnosis significantly reduced the subjective pain perception and the nociceptive flexion reflex. It also increased pain tolerance and reduced pain perception and the nociceptive reflex during the CPT. These effects were found only in highly susceptible subjects. However, the DNICs activity was less evident during hypnosis than during the CPT effects without hypnosis. Both hypnosis and DNICs were able to modify the perception of pain. It seems likely that DNICs and hypnosis use the same descending inhibitory pathways for the control of pain. The susceptibility of the subject is a critical factor in hypnotically induced analgesia.

Electroencephalography in the early diagnosis of HIV-related subacute encephalitis: analysis of 185 patients

Of subjects with asymptomatic HIV infection or Lymphoadenopathy Syndrome, 185 were studied by means of electroencephalography coupled with computerized spectral analysis and mapping (EEG-CSA). Abnormal EEGs were found in 30 of 118 (25.4%) patients with asymptomatic infection (CDC Group II) and in 20 of 67 (29.9%) patients with Lymphoadenopathy Syndrome (CDC Group III). The most common EEG abnormalities were represented by theta slowing on the frontal and fronto-temporal lobes and, in some cases, by delta slowing and paroxysmal sharp activity on the forebrain. Among 50 patients with abnormal EEGs, 16 showed some abnormalities on neuropsychological testing, whereas mild signs of cerebral atrophy were evident on CT scan in only 12 patients. These findings suggest that EEG-CSA could be a useful and sensitive method in the early detection and monitoring of HIV-related subacute encephalitis.

Trigeminofacial reflexes in primary headaches

Nociceptive processing in trigeminal system is likely to undergo to significant changes in chronic pain disorders such as in primary headache. The electrophysiological testing of brainstem reflexes seems to offer a valuable adjunct to the clinical evaluation, providing direct evidence for central dysmodulation of sensory and pain neurotransmission, i.e. dishabituation pattern and reduced pain threshold. We review the contribution of trigeminofacial reflex studies in the light of those recent data supporting the view of a dysfunctional sensory processing in primary headache.

Long-term evaluation of the effect of quetiapine on hallucinations, delusions and motor function in advanced Parkinson disease.

ObjectivesMental disorders (MDs) are disabling complications of Parkinson disease (PD). We set out to demonstrate the short- and long-term efficacy of quetiapine, an antipsychotic drug, in controlling hallucinations and delusions in parkinsonian patients without worsening their motor function. Since current guidelines recommend that dopaminergic drugs be decreased or even withdrawn altogether upon the appearance of MDs, we also sought to establish whether quetiapine enables a modification of this common course of action, and hence improve the management of pre-existing motor complications in affected subjects. MethodThirty-five PD patients with disabling MDs were enrolled in this open-label study. Motor function, MDs and cognitive state were evaluated before starting quetiapine therapy and after 1, 3, and 12 months of treatment. ResultsMDs significantly improved after 1, 3, and 12 months of quetiapine treatment. At the end of the study the mean daily dose of quetiapine (185 mg) did not produce significant changes in motor or cognitive function. Isolated hallucinations responded to low doses of quetiapine (110 mg daily), while delusions needed 265 mg daily. After 12 months, global dopaminergic therapy was reduced in 3 patients, modified (purely in terms of its components) in 17 patients, and increased in 15 patients. ConclusionsQuetiapine was effective in the treatment of hallucinations and delusions in PD. It did not worsen motor functions and allowed the dopaminergic treatment in PD patients affected by MDs to be managed safely.

Cerebrospinal fluid levels of tau phosphorylated at threonine 181 in patients with Alzheimer’s disease and vascular dementia

In 31 patients with probable Alzheimer’s disease (AD), 19 with probable vascular dementia (VaD) and 20 with Possible AD and Possible VaD, cerebrospinal fluid (CSF) tau levels hyperphosphorylated at threonine 181 (Ptau) were measured by ELISA. Thirty-six age-matched subjects were used as controls. The severity of the cognitive decline was assessed at the time of CSF analysis and after a 12-month follow-up. The groups had comparable age, degree of cognitive impairment and disease duration; these parameters were not related to P-tau levels. P-tau discriminated between demented patients and controls, but no significant difference emerged between AD and the other groups. By contrast, higher P-tau values were found to predict, independently of the clinical diagnosis, a more rapid evolution of cognitive decline. Whether these findings are due to a lack of CSF P-tau specificity or to the low reliability of clinical and radiological criteria remains unclear. P-tau may be useful in the evaluation of disease evolution, by predicting the rate of cognitive decline.