Papers by Grazia Palamara
Clinical Neuropharmacology, May 1, 2010
Tacrolimus has been often described to induce neuropathy in liver-, pancreas-, and renal-transpla... more Tacrolimus has been often described to induce neuropathy in liver-, pancreas-, and renal-transplanted patients. Here, we report the first case of a 56-year-old woman who developed a progressive symmetric demyelinating sensorimotor polyneuropathy in the distal muscles of the lower limbs after therapy with tacrolimus because of heart transplantation. This condition suddenly reverted after the tacrolimus was stopped.
Neurological Sciences, Mar 22, 2014
Archives of Physical Medicine and Rehabilitation, Jun 1, 2017
Land plus Aquatic therapy versus Land-based rehabilitation alone for the treatment of balance dys... more Land plus Aquatic therapy versus Land-based rehabilitation alone for the treatment of balance dysfunction in Parkinson's disease: a randomized, controlled study with 6-month follow-up.
XLII Congress of the Italian Neurological Society, 2011
Frontiers in Neuroscience, 2019
Freezing of gait (FoG) is a debilitating problem in patients with PD. The multifactorial pathogen... more Freezing of gait (FoG) is a debilitating problem in patients with PD. The multifactorial pathogenesis of FoG remains poorly understood. We aimed to find which factors are most strongly associated with the occurrence of FoG. Methods: Three hundred five PD patients were enrolled and subdivided according to the presence (FoG +, n = 128) or absence (FoG-, n = 177) of FoG. Several clinical, functional, and neuropsychological data were collected and compared between groups. The association between the probability of presence of FoG and possible explanatory variables was assessed by logistic regression analysis. Results: FoG + patients were younger at the diagnosis (p = 0.04), and their mean daily dose of dopaminergic drugs (p < 0.0001) was higher in comparison with FoGpatients. FoG + patients get worse in Frontal Assessment Battery (p = 0.005), had higher scores in Apathy Evaluation Scale (p = 0.03), and were much more impaired on Wisconsin Card Sorting Test (WCST) (p = 0.018), Trail Making Test A (p = 0.0013), and Ray Auditory Verbal Learning Test (p = 0.012). Levodopa equivalent dose, age (direct), age at disease onset (inverse), and WCST were significant predictors of FoG (p = 0.01, p = 0.0025, p = 0.0016, and p = 0.029, respectively). Conclusion: FoG + patients show more deficits in executive functions and in motivation. The main explanatory variables of FoG occurrence are levodopa equivalent dose, age, age at disease onset, and WCST. These data suggest that a specific involvement of frontal cortical circuits in PD is responsible for certain cognitivebehavioral alterations related to the occurrence of FoG.
Frontiers in Neurology, 2019
Background: constipation is one of the most common and disabling non-motor symptoms of Parkinson ... more Background: constipation is one of the most common and disabling non-motor symptoms of Parkinson Disease (PD) and Parkinsonisms (PS). Few studies evaluate the difference of prevalence between PD and PS and the cause leading to a severe constipation in this diseases. Objective: Aim of our study is to evaluate the prevalence of constipation in a population of patients with PD and PS and to evaluate which factors influence the development of severe constipation. Methods: Two hundred and fifty outpatients with PD and 39 with PS were enrolled. Sixty five age-matched healthy subjects served as control. Constipation was assessed using the "Constipation Scoring System" (CSS). All patients underwent a global clinical, functional and neuropsychological assessment including: Unified Parkinson's disease Rating Scale (UPDRS), 6-min Walk Test (6MWT), and Mini-Mental State Examination (MMSE). Results: Data confirm the high prevalence of constipation among patients with PD and PS. Severe constipation affects much more patients with PS. A significant association between total CSS and age, H and Y stage, 6MWT, MMSE, total UPDRS, and UPDRS III was found in PD. In PS patients total CSS was associated with age, 6MWT, total UPDRS, and UPDRS III. Multivariable regression analysis showed that the only variables significantly and independently associated with total CSS in PD patients were age and total UPDRS, both with direct relationship. The reduction of motor performance seems to be the primary cause for developing severe constipation in PD and PS patients. These data suggest that maintain a good quality of gait and endurance may be helpful to reduce the risk of constipation.
Toxicon, 2018
Introduction: Spastic equinus foot (EF) is common poststroke. Its mechanism can be diverse, inclu... more Introduction: Spastic equinus foot (EF) is common poststroke. Its mechanism can be diverse, including muscle overactivity, shortening of soft tissues, or both, which is most frequent. The aim of this study was to describe the causes of EF in a group of patients referred to the gait laboratory (GL). Methods: Poststroke patients with EF were evaluated between 2015 and 2018 in the GL of a neurorehabilitation center. This study analyzed findings regarding the sagittal angle of the ankle at initial contact and lower-limb muscle activation patterns during swing. Results: In a sample of 93 adult stroke survivors, 41 had EF in whom poor results had been achieved with botulinum toxin (BT) treatment or target muscles were not clear, or who might be candidates for surgery. Mean age was 49 years; 22 participants were female; 24 had right and 17 had left hemiparesis. Thirty-one patients also had hyperextension of the knee in stance. Deficits ranged from À2 to À25 (mean, À8) in the latter group and À2 to À13 (mean, À6) for cases with EF only. In the 41 participants, the muscles most frequently found to be actively out of phase were the soleus (54%), gastrocnemius lateralis (44%), gastrocnemius medialis, and tibialis posterior (34%). In 68%, EF patients were able to activate dorsiflexor muscles (tibialis anterior and/or extensor hallucis longus). Conclusions: In the study population of 41 patients with EF referred to the GL, lack of ankle dorsiflexion was due to overactivity of plantar flexion muscles or inability to overcome spasticity and/or stiffness of shortened soft tissues. The main cause for EF was apparently the shortening of plantar flexor muscles/tendons. In patients in whom we found no activation of the plantar flexors in swing, we concluded that there was no benefit in injecting them, hence avoiding a pointless intervention with its attendant risks and costs. The fact that 68% of cases were able to activate dorsiflexor muscles in swing allowed us to predict the need for ankle foot orthoses after BT or surgical treatment.
Frontiers in behavioral neuroscience, 2017
Rehabilitation for patients with Parkinson's disease (PD) is based on cognitive strategies th... more Rehabilitation for patients with Parkinson's disease (PD) is based on cognitive strategies that exploit attention. Parkinsonians exhibit impairments in divided attention and interference control. Nevertheless, the effectiveness of specific rehabilitation treatments based on attention suggests that other attentional functions are preserved. Data about attention are conflicting in PD, and it is not clear whether rehabilitative treatments that entail attentional strategies affect attention itself. Reaction times (RTs) represent an instrument to explore attention and investigate whether changes in attentional performances parallel rehabilitation induced-gains. RTs of 103 parkinsonian patients in "on" state, without cognitive deficits, were compared with those of a population of 34 healthy controls. We studied those attentional networks that subtend the use of cognitive strategies in motor rehabilitation: alertness and focused and sustained attention, which is a component o...
SAGE Open Medical Case Reports, 2017
Objective: To report a rare case of hypokalemic rhabdomyolysis induced by the heavy and prolonged... more Objective: To report a rare case of hypokalemic rhabdomyolysis induced by the heavy and prolonged ingestion of colabased beverages, and its uneventful recovery after kalemia normalization. Methods: We report a 38-year-old Caucasian male presented in our emergency room with a recent and progressive weakness of the lower limbs proximal muscles. Results: A dietary history revealed a prolonged ingestion of cola-based beverages. Blood tests showed severe hypokalemia and marked increase in serum creatine phosphokinase. The analysis of cerebrospinal fluid resulted normal. Electromyography was suggestive for a myopathy. The clinical, laboratory and neurophysiological data were evocative for a cola-induced hypokalemic rhabdomyolysis. After kalemia normalization, the improvements of the electromyographic findings paralleled the clinical recovery. Conclusion: Chronic consumption of large amount of cola-based soft drinks may result in severe symptomatic hypokalemia, eventually leading in turn to myopathy. To our knowledge, this is the first description of the electromyographic findings of the colainduced hypokalemic rhabdomyolysis. An early diagnosis and a prompt treatment appear to be crucial for a benign clinical course.
Frontiers in Behavioral Neuroscience, 2016
The principal feature of Parkinson's disease (PD) is the impaired ability to acquire and express ... more The principal feature of Parkinson's disease (PD) is the impaired ability to acquire and express habitual-automatic actions due to the loss of dopamine in the dorsolateral striatum, the region of the basal ganglia associated with the control of habitual behavior. Dopamine replacement therapy (DRT) compensates for the lack of dopamine, representing the standard treatment for different motor symptoms of PD (such as rigidity, bradykinesia and resting tremor). On the other hand, rehabilitation treatments, exploiting the use of cognitive strategies, feedbacks and external cues, permit to "learn to bypass" the defective basal ganglia (using the dorsolateral area of the prefrontal cortex) allowing the patients to perform correct movements under executive-volitional control. Therefore, DRT and rehabilitation seem to be two complementary and synergistic approaches. Learning and reward are central in rehabilitation: both of these mechanisms are the basis for the success of any rehabilitative treatment. Anyway, it is known that "learning resources" and reward could be negatively influenced from dopaminergic drugs. Furthermore, DRT causes different well-known complications: among these, dyskinesias, motor fluctuations, and dopamine dysregulation syndrome (DDS) are intimately linked with the alteration in the learning and reward mechanisms and could impact seriously on the rehabilitative outcomes. These considerations highlight the need for careful titration of DRT to produce the desired improvement in motor symptoms while minimizing the associated detrimental effects. This is important in order to maximize the motor re-learning based on repetition, reward and practice during rehabilitation. In this scenario, we review the knowledge concerning the interactions between DRT, learning and reward, examine the most impactful DRT side effects and provide suggestions for optimizing rehabilitation in PD.
BioMed Research International, 2015
Balance dysfunctions are a major challenge in the treatment of Parkinson’s disease (PD). Previous... more Balance dysfunctions are a major challenge in the treatment of Parkinson’s disease (PD). Previous studies have shown that rehabilitation can play a role in their treatment. In this study, we have compared the efficacy of two different devices for balance training: stabilometric platform and crossover. We have enrolled 60 PD patients randomly assigned to two groups. The first one (stabilometric group) performed a 4-week cycle of balance training, using the stabilometric platform, whereas the second one (crossover group) performed a 4-week cycle of balance training, using the crossover. The outcome measures used were Unified Parkinson’s Disease Rating Scale (UPDRS) part II, Berg Balance Scale (BBS), Timed Up and Go (TUG), and Six Minutes Walking Test (6MWT). Results showed that TUG, BBS, and UPDRS II improved in both groups. There was not difference in the efficacy of the two balance treatments. Patients in both groups improved also the meters walked in the 6MWT at the end of rehabili...
Parkinson's Disease, 2015
Balance dysfunction (BD) in Parkinson’s disease (PD) is a disabling symptom, difficult to treat a... more Balance dysfunction (BD) in Parkinson’s disease (PD) is a disabling symptom, difficult to treat and predisposing to falls. The dopaminergic drugs or deep brain stimulation does not always provide significant improvements of BD and rehabilitative approaches have also failed to restore this condition. In this study, we investigated the suitability of quantitative posturographic indicators to early identify patients that could develop disabling BD. Parkinsonian patients not complaining of a subjective BD and controls were tested using a posturographic platform (PP) with open eyes (OE) and performing a simple cognitive task [counting (OEC)]. We found that patients show higher values of total standard deviation (SD) of body sway and along the medio-lateral (ML) axis during OE condition. Furthermore, total and ML SD of body sway during OE condition and total SD of body sway with OEC were higher than controls also in a subgroup of patients with normal Berg Balance Scale. We conclude that B...
Epilepsy Research, 2013
Mutations of PRRT2, which encodes proline-rich transmembrane protein 2, are associated with heter... more Mutations of PRRT2, which encodes proline-rich transmembrane protein 2, are associated with heterogeneous phenotypes including benign familial infantile seizures (BFIS) and/or familial paroxysmal kinesigenic dystonia (PKD). Here, we performed mutation screening of PRRT2 in six Italian families with BFIS/PKD phenotypes. The mutation, c.649dupC (p.Arg217ProfsX8), was found in two families with BFIS phenotype. In a third BFIS family, a missense mutation, c.718C/T (R240X), was identified. All these mutations co-segregated with the disease and were not observed in 100 controls of matched ancestry. In one BFIS family that carried the c.649dupC mutation, one affected member developed afebrile focal seizures and died at age of 14 years of probable sudden unexpected death in epilepsy, while his brother also had simple febrile convulsions (FC) and performed poorly on complex psychomotor functioning. In another family carrying the c.718C/T mutation, two of three affected members also had simple FC. This study enlarges the clinical spectrum related to PPRT2 mutations and underscores the complexity of the phenotypic consequences of mutations in this gene.
Annals of Human Genetics, 2012
The 1354C&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp... more The 1354C&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;T polymorphism of the 5-hydroxytryptamine receptor 2A gene (5-HTR2A) was implicated in human memory performance. We investigated the relationship between this polymorphism and cognitive function in patients with temporal lobe epilepsy (TLE). We also evaluated if this polymorphism could influence the phenotype. There were 138 patients with TLE: 25% (34/138) of them found to be cognitively impaired, while the remaining 104 of 138 (75%) were found to be cognitively preserved after a comprehensive neuropsychological evaluation. dHPLC followed by DNA sequencing was used to detect the genetic variation. The distribution of 1354C&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;T did not differ between these two TLE groups, both in the comparison of genotype distribution (P= 0.177) and allele frequencies (P = 0.065). Nonetheless, patients with the T allele had a significantly earlier age at onset of the disease (P= 0.006). This effect was even stronger in patients with impaired memory (P= 0.00015). A second independent sample of 86 individuals with TLE satisfactorily confirmed the relationship between T allele and age at epilepsy onset. The results of this study have demonstrated that the T variant of 5-HTR2A may influence an earlier age of onset of TLE, especially in those with impaired memory. Nonetheless, this polymorphism has no major impact on memory functions in such TLE patients.
Clinical Neuropharmacology, 2010
Tacrolimus has been often described to induce neuropathy in liver-, pancreas-, and renal-transpla... more Tacrolimus has been often described to induce neuropathy in liver-, pancreas-, and renal-transplanted patients. Here, we report the first case of a 56-year-old woman who developed a progressive symmetric demyelinating sensorimotor polyneuropathy in the distal muscles of the lower limbs after therapy with tacrolimus because of heart transplantation. This condition suddenly reverted after the tacrolimus was stopped.
Neurological Sciences, 2014
A variety of autoimmune etiologies such as anti-LGI1 encephalitis and anti-N-methyl-D-aspartic ac... more A variety of autoimmune etiologies such as anti-LGI1 encephalitis and anti-N-methyl-D-aspartic acid receptor (anti-NMDAR) are being increasingly recognized as causes of encephalitis in children and adolescent [1, 2]. Although many cases of autoimmune encephalitis (AE) remain seronegative considering the available antibodies tests, the diagnosis of probable AE is suggested by a combination of clinical, MRI and CSF findings [1]. Furthermore, the diagnosis is also proposed by exclusion of central nervous system infectious, metabolic, toxic disorders and it is often considered late especially in serologically negative subjects [1]. In such cases early abnormal MRI signals in the mesial temporal lobes, either unilaterally or bilaterally, may help raise the index of suspicion. Here we report a child affected by a probable AE who developed a symmetrical external capsule hyperintensity 2 weeks after the onset of illness that disappeared at followup after immunotherapy. A 14-year-old boy presented to our clinic because of an unexpected onset of status epilepticus. He had neither remarkable history of personal antecedents nor epilepsy and family history of epilepsy. Ten days before the onset he displayed encephalitis-like symptoms characterized by fever, headache, drowsiness, and confusion. Seizures manifested with initial visual disturbance (the perception of red balls on the left side) followed by loss of consciousness, left deviation of face and eyes evolving into generalized convulsions. The stereotyped seizure lasted for 5 min and appeared every few minutes. At admission, he was afebrile but confused with recurrent seizures. He underwent a prolonged video-electroencephalogram monitoring (vEEG) that revealed focal rhythmic spikes at 5–10 Hz in the right occipital region spreading into generalized activity during ictal EEG activity. Diffuse delta background slowing was seen during interictal periods. His status epilepticus was suddenly treated with high dose of valproate (VPA; 2,400 mg/day 100/mg/h) plus continuous infusion of midazolam (MDZ; 0.5 mg/kg/h) both intravenously infused without success. An extensive blood analysis and cerebrospinal fluid (CSF) analysis, autoantibody testing (e.g. anti-nuclear, anti-Ro, GAD, classical onconeuronal antibodies, antibodies against N-methyl-D-aspartate receptor, voltagegated potassium channel complex proteins, contactinassociated protein-2, LGI1, Caspr2, GABAb, AMPAR1, AMPAR2) and detailed neuroimaging (MRI) with an epilepsy protocol were performed. Blood analysis (for viral and bacterial agents) and autoantibody search were normal whereas CSF analysis revealed a mild pleiocitosis (\50 cells/mm) with oligoclonal bands and was negative for viral and bacterial agents. Abdominal, pelvic and scrotal ultrasound as well as chest computer tomography was normal. Extensive L. Mumoli and A. Labate equally contributed to the study.
Parkinson's Disease, 2015
Balance dysfunction (BD) in Parkinson's disease (PD) is a disabling symptom, difficult to treat a... more Balance dysfunction (BD) in Parkinson's disease (PD) is a disabling symptom, difficult to treat and predisposing to falls. The dopaminergic drugs or deep brain stimulation does not always provide significant improvements of BD and rehabilitative approaches have also failed to restore this condition. In this study, we investigated the suitability of quantitative posturographic indicators to early identify patients that could develop disabling BD. Parkinsonian patients not complaining of a subjective BD and controls were tested using a posturographic platform (PP) with open eyes (OE) and performing a simple cognitive task [counting (OEC)]. We found that patients show higher values of total standard deviation (SD) of body sway and along the medio-lateral (ML) axis during OE condition. Furthermore, total and ML SD of body sway during OE condition and total SD of body sway with OEC were higher than controls also in a subgroup of patients with normal Berg Balance Scale. We conclude that BD in Parkinsonian patients can be discovered before its appearance using a PP and that these data may allow developing specific rehabilitative treatment to prevent or delay their onset.
BioMed Research International, 2015
Balance dysfunctions are a major challenge in the treatment of Parkinson's disease (PD). Previous... more Balance dysfunctions are a major challenge in the treatment of Parkinson's disease (PD). Previous studies have shown that rehabilitation can play a role in their treatment. In this study, we have compared the efficacy of two different devices for balance training: stabilometric platform and crossover. We have enrolled 60 PD patients randomly assigned to two groups. The first one (stabilometric group) performed a 4-week cycle of balance training, using the stabilometric platform, whereas the second one (crossover group) performed a 4-week cycle of balance training, using the crossover. The outcome measures used were Unified Parkinson's Disease Rating Scale (UPDRS) part II, Berg Balance Scale (BBS), Timed Up and Go (TUG), and Six Minutes Walking Test (6MWT). Results showed that TUG, BBS, and UPDRS II improved in both groups. There was not difference in the efficacy of the two balance treatments. Patients in both groups improved also the meters walked in the 6MWT at the end of rehabilitation, but the improvement was better for patients performing crossover training. Our results show that the crossover and the stabilometric platform have the same effect on balance dysfunction of Parkinsonian patients, while crossover gets better results on the walking capacity.
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Papers by Grazia Palamara