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Papers by Francesca Pastorelli

Health and Gender, 2019

There is increasing attention on determinants of health including not only the genetic and biolog... more There is increasing attention on determinants of health including not only the genetic and biological differences between males and females defining what we usually call “sex” but also psychological, environmental, and sociocultural factors that define what is commonly called “gender” and which may affect disproportionally men’s and women’s health.

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Journal of Neurology, 2020

Background Diagnostic delay of hereditary transthyretin amyloidosis (ATTRv, v for variant) preven... more Background Diagnostic delay of hereditary transthyretin amyloidosis (ATTRv, v for variant) prevents timely treatment and, therefore, concurs to the mortality of the disease. The aim of the present study was to explore with nerve ultrasound (US) possible red flags for early diagnosis in ATTRv patients with carpal tunnel syndrome (CTS) and/or polyneuropathy and in pre-symptomatic carriers. Methods Patients and pre-symptomatic carriers with a TTR gene mutation were enrolled from seven Italian centers. Severity of CTS was assessed with neurophysiology and clinical evaluation. Median nerve cross-section area (CSA) was measured with US in ATTRv carriers with CTS (TTR-CTS). One thousand one hundred ninety-six idiopathic CTS were used as controls. Nerve US was also performed in several nerve trunks (median, ulnar, radial, brachial plexi, tibial, peroneal, sciatic, sural) in ATTRv patients with polyneuropathy and in pre-symptomatic carriers. Results Sixty-two subjects (34 men, 28 women, mean...

Journal of the Peripheral Nervous System, 2019

People interested in the research are advised to contact the author for the final version of the ... more People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website. • The final author version and the galley proof are versions of the publication after peer review. • The final published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal. If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the "Taverne" license above, please follow below link for the End User Agreement:

Clinical Neurophysiology, 2014

Methods: Description of a case series. Eight NF1 patients underwent interventions in order to rem... more Methods: Description of a case series. Eight NF1 patients underwent interventions in order to remove spinal roots neurofibromas causing cervical spinal cord compression. A second intervention at the lumbosacral spine was necessary to remove neurofibromas located at the cauda equina in 2 cases. In all cases, IONM by means of motor evoked potentials (MEPs), somatosensory evoked potentials (SSEPs, epidural SSEPs), D-Wave monitoring and Bulbocavernosus Reflex (BCR) was performed. Additionally, in order to identify motor nerve roots and to preserve their function during surgery, neural tissues mapping was performed by direct electrical stimulation of the structures with a bipolar probe. Results: A total of 54 neurofibromas at the cervical and lumbosacral spine were removed. Motor nerve roots were identified and subtotally resected, sparing rootlets with small tumour nodules. Tumours on sensitive nerve roots were fully resected. When tumours were located at the cauda equina, nerve roots were also monitored using a train of stimulus to determine if these sensitive roots were critically involved in BCR. BCR was successfully elicited in both patients with tumours involving cauda equina and were preserved after tumour removing. No significant changes occurred in MEPs, SSEPs or D-Wave monitoring during surgeries. Conclusions: IONM provides continuous, real-time information about the function of neural pathways at risk during surgery and helps the surgeon to identify motor neural structures. The importance of BCR for the clinical outcome of the patients requires the use of special techniques intended to intraoperatively maintain the reflex. As opposed to schwannomas, neurofibromas grow encasing neural fibres from motor and sensory nerve roots. Subtotal resection should be performed in motor roots in order to preserve motor function.

Clinical Neurophysiology, 2014

s of Poster Presentations / Clinical Neurophysiology 125, Supplement 1 (2014) S1–S339 S303 were n... more s of Poster Presentations / Clinical Neurophysiology 125, Supplement 1 (2014) S1–S339 S303 were normal, bacterial and viral infections were excluded. ENG showed severe axonal motor nerve neuropathy. Porphyrin and protoporphyrin from blood proved acute intermittent porphyria. Neurological symptoms recovered after hemin infusion. The second patient was a 17-year old female, admitted with ascending type of tetraparesis, without fever, or bacterial viral infection. After some days, urinary retention developed. Intracranial and spinal MRI were negative. On admission ENG showed moderate axonal motor and sensory neuropathy in the lower limbs. After clinical progression, severe sensory predominant sensomotor polyneuropathy with the suspicion of radiculopathy in all limbs was detected. Immunological tests (pANCA, cANCA, anti-gangliozid, antinuclear antibodies), serology were negative. The amount of B-type cells and IgM was higher. Sudden heart failure caused death. Autopsy and histology showed no signs of inflammation. The final diagnosis was thought to be acute motor-sensory axonal neuropathy. Conclusion: ENG/EMG helps us to more precise, fast diagnosis and followup, in order to start the appropriate therapy. P959 Clinical and neurophysiological spectrum of peripheral neurotoxicity in patients with CD30-positive malignancies, treated with Brentuximab Vedotin F. Pastorelli, R. Plasmati, F. Salvi IRCCS Istituto delle Scienze Neurologiche, O. Bellaria, Bologna, Italy Objective: To describe the clinical and neurophysiological spectrum of neurotoxic peripheral motor involvement in patients treated with Brentuximab Vedotin. Background: Brentuximab Vedotin is an antibody-drug conjugate composed by the anti-CD30 chimeric IgG1 monoclonal antibody cAC10 and the antimicrotubule drug monomethyllauristatin E. Brentuximab vedotin is effective as a single-agent therapy for the treatment of relapsed or refractory CD30-positive malignancies such as classical Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). Peripheral sensory neuropathy, grade 1 or 2 in severity, seems to be one of the most frequent adverse events. Grade 3 motor neuropathy is believed to be present only in a minority of patients. Discontinuation of treatment may be followed by improvement of the neurologic symptoms, but complete regression of the neuropathy is not the rule. Case reports: We studied 7 patients treated with Brentuximab Vedotin for HL who developed a sensory-motor neuropathy. The degree of motor involvement varied from mild hyposthenia prevalent in distal muscles of the limbs to severe upper limb diplegia, mimicking motor neuron disease. The sensory-motor conduction study show principally a reduction of sensory-motor conduction velocities, with SAP and cMAP amplitudes reduced. Some patients, however, developed severe reduction of the amplitudes of proximal cMAPs resembling motor conduction blocks. The needle EMG study showed acute denervation in weak muscles, with high amplitude, polyphasic MUPs producing a less-than-full interference pattern. The discontinuation of the treatment and repeated plasmapheresis have been followed in our patients by progressive improvement of muscle strength. Conclusions: Peripheral nerve neurotoxicity is a well known event in patients treated with antimicrotubule drugs and motor involvement is also possible, with severe impact on patients’ quality of life. More studies are needed to assess the incidence of peripheral neurotoxicity, the clinical and neurophysiological pattern of the neuropathy, the rate of reversibility and the presence of risk factors for grade 3-4 neurotoxicity. P961 Case report: post herpetic motor plexopathy in a patient suffering for multiple myeloma R. Sans-Boza, E. Villamil Plymouth Hospitals NHS Trust, Neurophysiology, Plymouth, United Kingdom Case report of a 59 year old in treatment for multiple myeloma, that suffered a severe herpes zoster infection in the left brachial plexus territory. 3 weeks after symptoms onset he developed severe weakness of muscles in the shoulder girdle as well as sesnory symptoms like paresthesiae in both hands and forearms. NCS and EMG examination was undertaken. Nerve conduction tests showed increased distal motor and sensory latencies in the median nerves. There was no reproducible motor response from biceps when stimulating the left musculocutaneous nerve, and the response from Deltoid when stimualting the left axillary nerve was very low in amplitude. The contralateral motor responses were normal. EMG showed a severe pattern of acute dennervation without volitional activity in the left biceps brachii muscle. Left Deltoid and Infraspinatus showed also signs of acute dennervation but some volitional activity was preserved. Left Upper Trapezius, Triceps and pronator teres showed largely normal EMG features. After extensive questioning the patient admitted to sensory symptoms in his hands prior to the herpetic infection. However, there were no other…

Neurology, 2004

The clinical and neurophysiologic data from 65 patients taking thalidomide were reviewed. Thalido... more The clinical and neurophysiologic data from 65 patients taking thalidomide were reviewed. Thalidomide sensory neurotoxicity was found to be cumulative dose dependent but occurs only when the total dose is relatively high (>20 g). The risk of developing sensory neuropathy is around 10% below this threshold but increases with higher doses.

European Spine Journal, 2015

PurposeCombined intraoperative monitoring (IOM) of transcranial electric motor-evoked potentials ... more PurposeCombined intraoperative monitoring (IOM) of transcranial electric motor-evoked potentials (tce-MEPs) and somatosensory-evoked potentials (SSEPs) is safe and effective for spinal cord monitoring during scoliosis surgery. However, the literature data regarding the reliability of spinal cord monitoring in patients with neuromuscular scoliosis are conflicting and need to be confirmed.MethodsWe reviewed IOM records of 40 consecutive patients with neuromuscular scoliosis related to central nervous system (CNS) (29 pts) or peripheral nervous system (PNS) (11 patients) diseases, who underwent posterior fusion with instrumentation surgery for spinal deformity. Multimodalitary IOM with SSEPs and tce-MEPs was performed.ResultsSpinal cord monitoring using at least one modality was attempted in 38/40 (95 %) patients. No false-negative results were present in either group, but a relatively high incidence of false-positive cases (4/29, 13.8 %) was noted in the CNS group. Two patients in the CNS group and one patient in the PNS group presented transient postoperative motor deficits (true positive), related to surgical manoeuvres in two cases and to malposition in the other one.ConclusionsMultimodalitary IOM is safe and effective to detect impending spinal cord and peripheral nerves dysfunction in neuromuscular scoliosis surgery. However, the interpretation of neurophysiological data may be challenging in such patients, and the rate of false-positive results is high when pre-operatory motor deficits are severe.

Journal of Neurology

Background Assessing the safety of SARS-CoV-2 mRNA vaccines and the effect of immunotherapies on ... more Background Assessing the safety of SARS-CoV-2 mRNA vaccines and the effect of immunotherapies on the seroconversion rate in patients with autoimmune neurological conditions (ANC) is relevant to clinical practice. Our aim was to assess the antibody response to and safety of SARS-CoV-2 mRNA vaccines in ANC. Methods This longitudinal study included ANC patients vaccinated with two doses of BNT162b2 or mRNA-1273 between March and August 2021. Side effects were assessed 2-10 days after each dose. Neurological status and anti-spike receptor binding domain antibody levels were evaluated before vaccination and 4 weeks after the second dose. Healthcare-workers served as controls for antibody levels. Results We included 300 ANC patients (median age 52, IQR 40-65), and 347 healthcare-workers (median age 45, IQR 34-54). mRNA-1273 vaccine was associated with an increased risk of both local (OR 2.52 95% CI 1.45-4.39, p = 0.001) and systemic reactions (OR 2.51% CI 1.49-4.23, p = 0.001). The incidence of relapse was not different before and after vaccine (Incidence rate ratio 0.72, 95% CI 0.29-1.83). Anti-SARS-CoV-2 IgG were detected in 268 (89.9%) patients and in all controls (p < 0.0001). BNT162b2 vaccine (OR 8.84 95% CI 2.32-33.65, p = 0.001), anti-CD20 mAb (OR 0.004 95% CI 0.0007-0.026, p < 0.0001) and fingolimod (OR 0.036 95% CI 0.002-0.628, p = 0•023) were associated with an increased risk of not developing anti-SARS-CoV-2 IgG. Conclusion SARS-CoV-2 mRNA vaccines were safe in a large group of ANC patients. Anti-CD20 and fingolimod treatment, as well as vaccination with the BNT162b2 vaccine, led to a reduced humoral response. These findings could inform vaccine policies in ANC patients undergoing immunotherapy.

Neurology, 2014

OBJECTIVE To describe the clinical and neurophysiological spectrum of neurotoxic peripheral motor... more OBJECTIVE To describe the clinical and neurophysiological spectrum of neurotoxic peripheral motor involvement in patients treated with Brentuximab Vedotin. BACKGROUND Brentuximab Vedotin is an antibody-drug conjugate composed by the anti-CD30 chimeric IgG1 monoclonal antibody cAC10 and the antimicrotubule drug monomethyllauristatin E. Brentuximab vedotin is effective as a single-agent therapy for the treatment of relapsed or refractory CD30-positive malignancies such as classical Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). Peripheral sensory neuropathy, grade 1 or 2 in severity, seems to be one of the most frequent adverse events. Grade 3 motor neuropathy is believed to be present only in a minority of patients. Discontinuation of treatment may be followed by improvement of the neurologic symptoms, but complete regression of the neuropathy is not the rule. CASE REPORTS We studied 7 patients treated with Brentuximab Vedotin for HL who developed a sensory-motor ne...

Neurology, 2014

BACKGROUND IncobotulinumtoxinA (Xeomin ®), a botulinum toxin type A drug without complexing prote... more BACKGROUND IncobotulinumtoxinA (Xeomin ®), a botulinum toxin type A drug without complexing proteins, became available in 2005. To our knowledge, this is the first randomized controlled double blind trial comparing the therapeutic effect of two non-bioequivalent toxins: IncobotulinumtoxinA and AbobotulinumtoxinA (Dysport ®) for treatment of primary axillary hyperhidrosis. METHODS: Twenty patients with primary axillary hyperhidrosis were treated with IncobotulinumtoxinA injections into one axilla and AbobotulinumtoxinA injections into the other axilla. Both patients and the physician were blinded as to which axilla received which of the two toxins. IncobotulinumtoxinA, 100 IU, and AbobotulinumtoxinA, 500IU, were diluted in 5 mL of 0.9% saline each. A total of 50 IU of IncobotulinumtoxinA or 250IU of AbobotulinumtoxinA was injected. Pain at the injection site has been evaluated by the VAS scale. A twelve month follow up is scheduled to evaluate the difference between these two toxins ...

European Journal of Cancer, 2013

Chemotherapy-induced peripheral neuropathy (CIPN) is a common neurological side-effect of cancer ... more Chemotherapy-induced peripheral neuropathy (CIPN) is a common neurological side-effect of cancer treatment and may lead to declines in patients' daily functioning and quality of life. To date, there are no modern clinimetrically well-evaluated outcome measures available to assess disability in CIPN patients. The objective of the study was to develop an interval-weighted scale to capture activity limitations and participation restrictions in CIPN patients using the Rasch methodology and to determine its validity and reliability properties. A preliminary Rasch-built Overall Disability Scale (pre-RODS) comprising 146 items was assessed twice (interval: 2-3 weeks; test-retest reliability) in 281 CIPN patients with a stable clinical condition. The obtained data were subjected to Rasch analyses to determine whether model expectations would be met, and if necessarily, adaptations were made to obtain proper model fit (internal validity). External validity was obtained by correlating the CIPN-RODS with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) neuropathy scales and the Pain-Intensity Numeric-Rating-Scale (PI-NRS). The preliminary RODS did not meet Rasch model's expectations. Items displaying misfit statistics, disordered thresholds, item bias or local dependency were systematically removed. The final CIPN-RODS consisting of 28 items fulfilled all the model's expectations with proper validity and reliability, and was unidimensional. The final CIPN-RODS is a Rasch-built disease-specific, interval measure suitable to detect disability in CIPN patients and bypasses the shortcomings of classical test theory ordinalbased measures. Its use is recommended in future clinical trials in CIPN.

Annals of Neurology, 2005

based on a thorough search of the medical literature and a poison control center consultation. Ta... more based on a thorough search of the medical literature and a poison control center consultation. Tamoxifen infrequently causes reversible neurotoxicity, but only at much higher doses (Ն160mg/m 2 daily). 5 Recent investigations into the use of artemisinin compounds in cancer treatment 6 have not been substantiated in clinical trials. Because of pervasive reports of animal brainstem toxicity, and the gradual emergence of similar patient cases, it becomes imperative to ascertain the safety of prolonged courses of artemisinin for cancer prophylaxis.

Amyloid, 2021

Abstract Background Ile68Leu transthyretin-related amyloidosis (ATTR) is known as a mainly or exc... more Abstract Background Ile68Leu transthyretin-related amyloidosis (ATTR) is known as a mainly or exclusively cardiogenic variant. We hypothesized that an accurate specialized neurological evaluation could reveal a consistent frequency of mixed phenotypes. Methods Forty-six consecutive subjects with transthyretin (TTR) Ile68Leu (p.Ile88Leu) mutation (29 patients and 17 unaffected carriers) underwent an in-depth cardiac and neurologic evaluation at a single center. Results All 29 patients showed cardiac involvement. In 20 (69%) cases, it was associated with neurological abnormalities (i.e. a mixed phenotype): 10 (35% of the total) had signs and symptoms of neuropathy, 5 (17%) had abnormalities at the neurologic specialist examination but without symptoms, and 5 (17%) had abnormal nerve conduction study only. None of the asymptomatic carriers showed neurological abnormalities or cardiac involvement. The Neuropathy Impairment Score was > 5 in seven patients at baseline, and became >5 in six more patients during follow-up. The probability of experiencing a major adverse cardiac event (MACE) during follow-up was higher in the mixed than cardiologic phenotype (p = 0.026). Age and phenotype were independent prognostic predictors of MACE. Conclusion At least two-thirds of patients with Ile68Leu ATTR and amyloidotic cardiomyopathy show an associated – definite or probable – neurologic impairment of variable degree if accurately evaluated in a neurologic setting. This proportion can rise during follow-up. The mixed phenotype carries a worse prognosis compared to the exclusively cardiologic one. These observations show that more patients could be eligible for treatment with gene silencers than currently indicated and highlight the need for an in-depth and continuous multidisciplinary evaluation of Ile68Leu ATTR patients.

Health and Gender, 2019

There is increasing attention on determinants of health including not only the genetic and biolog... more There is increasing attention on determinants of health including not only the genetic and biological differences between males and females defining what we usually call “sex” but also psychological, environmental, and sociocultural factors that define what is commonly called “gender” and which may affect disproportionally men’s and women’s health.

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Journal of Neurology, 2020

Background Diagnostic delay of hereditary transthyretin amyloidosis (ATTRv, v for variant) preven... more Background Diagnostic delay of hereditary transthyretin amyloidosis (ATTRv, v for variant) prevents timely treatment and, therefore, concurs to the mortality of the disease. The aim of the present study was to explore with nerve ultrasound (US) possible red flags for early diagnosis in ATTRv patients with carpal tunnel syndrome (CTS) and/or polyneuropathy and in pre-symptomatic carriers. Methods Patients and pre-symptomatic carriers with a TTR gene mutation were enrolled from seven Italian centers. Severity of CTS was assessed with neurophysiology and clinical evaluation. Median nerve cross-section area (CSA) was measured with US in ATTRv carriers with CTS (TTR-CTS). One thousand one hundred ninety-six idiopathic CTS were used as controls. Nerve US was also performed in several nerve trunks (median, ulnar, radial, brachial plexi, tibial, peroneal, sciatic, sural) in ATTRv patients with polyneuropathy and in pre-symptomatic carriers. Results Sixty-two subjects (34 men, 28 women, mean...

Journal of the Peripheral Nervous System, 2019

People interested in the research are advised to contact the author for the final version of the ... more People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website. • The final author version and the galley proof are versions of the publication after peer review. • The final published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal. If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the "Taverne" license above, please follow below link for the End User Agreement:

Clinical Neurophysiology, 2014

Methods: Description of a case series. Eight NF1 patients underwent interventions in order to rem... more Methods: Description of a case series. Eight NF1 patients underwent interventions in order to remove spinal roots neurofibromas causing cervical spinal cord compression. A second intervention at the lumbosacral spine was necessary to remove neurofibromas located at the cauda equina in 2 cases. In all cases, IONM by means of motor evoked potentials (MEPs), somatosensory evoked potentials (SSEPs, epidural SSEPs), D-Wave monitoring and Bulbocavernosus Reflex (BCR) was performed. Additionally, in order to identify motor nerve roots and to preserve their function during surgery, neural tissues mapping was performed by direct electrical stimulation of the structures with a bipolar probe. Results: A total of 54 neurofibromas at the cervical and lumbosacral spine were removed. Motor nerve roots were identified and subtotally resected, sparing rootlets with small tumour nodules. Tumours on sensitive nerve roots were fully resected. When tumours were located at the cauda equina, nerve roots were also monitored using a train of stimulus to determine if these sensitive roots were critically involved in BCR. BCR was successfully elicited in both patients with tumours involving cauda equina and were preserved after tumour removing. No significant changes occurred in MEPs, SSEPs or D-Wave monitoring during surgeries. Conclusions: IONM provides continuous, real-time information about the function of neural pathways at risk during surgery and helps the surgeon to identify motor neural structures. The importance of BCR for the clinical outcome of the patients requires the use of special techniques intended to intraoperatively maintain the reflex. As opposed to schwannomas, neurofibromas grow encasing neural fibres from motor and sensory nerve roots. Subtotal resection should be performed in motor roots in order to preserve motor function.

Clinical Neurophysiology, 2014

s of Poster Presentations / Clinical Neurophysiology 125, Supplement 1 (2014) S1–S339 S303 were n... more s of Poster Presentations / Clinical Neurophysiology 125, Supplement 1 (2014) S1–S339 S303 were normal, bacterial and viral infections were excluded. ENG showed severe axonal motor nerve neuropathy. Porphyrin and protoporphyrin from blood proved acute intermittent porphyria. Neurological symptoms recovered after hemin infusion. The second patient was a 17-year old female, admitted with ascending type of tetraparesis, without fever, or bacterial viral infection. After some days, urinary retention developed. Intracranial and spinal MRI were negative. On admission ENG showed moderate axonal motor and sensory neuropathy in the lower limbs. After clinical progression, severe sensory predominant sensomotor polyneuropathy with the suspicion of radiculopathy in all limbs was detected. Immunological tests (pANCA, cANCA, anti-gangliozid, antinuclear antibodies), serology were negative. The amount of B-type cells and IgM was higher. Sudden heart failure caused death. Autopsy and histology showed no signs of inflammation. The final diagnosis was thought to be acute motor-sensory axonal neuropathy. Conclusion: ENG/EMG helps us to more precise, fast diagnosis and followup, in order to start the appropriate therapy. P959 Clinical and neurophysiological spectrum of peripheral neurotoxicity in patients with CD30-positive malignancies, treated with Brentuximab Vedotin F. Pastorelli, R. Plasmati, F. Salvi IRCCS Istituto delle Scienze Neurologiche, O. Bellaria, Bologna, Italy Objective: To describe the clinical and neurophysiological spectrum of neurotoxic peripheral motor involvement in patients treated with Brentuximab Vedotin. Background: Brentuximab Vedotin is an antibody-drug conjugate composed by the anti-CD30 chimeric IgG1 monoclonal antibody cAC10 and the antimicrotubule drug monomethyllauristatin E. Brentuximab vedotin is effective as a single-agent therapy for the treatment of relapsed or refractory CD30-positive malignancies such as classical Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). Peripheral sensory neuropathy, grade 1 or 2 in severity, seems to be one of the most frequent adverse events. Grade 3 motor neuropathy is believed to be present only in a minority of patients. Discontinuation of treatment may be followed by improvement of the neurologic symptoms, but complete regression of the neuropathy is not the rule. Case reports: We studied 7 patients treated with Brentuximab Vedotin for HL who developed a sensory-motor neuropathy. The degree of motor involvement varied from mild hyposthenia prevalent in distal muscles of the limbs to severe upper limb diplegia, mimicking motor neuron disease. The sensory-motor conduction study show principally a reduction of sensory-motor conduction velocities, with SAP and cMAP amplitudes reduced. Some patients, however, developed severe reduction of the amplitudes of proximal cMAPs resembling motor conduction blocks. The needle EMG study showed acute denervation in weak muscles, with high amplitude, polyphasic MUPs producing a less-than-full interference pattern. The discontinuation of the treatment and repeated plasmapheresis have been followed in our patients by progressive improvement of muscle strength. Conclusions: Peripheral nerve neurotoxicity is a well known event in patients treated with antimicrotubule drugs and motor involvement is also possible, with severe impact on patients’ quality of life. More studies are needed to assess the incidence of peripheral neurotoxicity, the clinical and neurophysiological pattern of the neuropathy, the rate of reversibility and the presence of risk factors for grade 3-4 neurotoxicity. P961 Case report: post herpetic motor plexopathy in a patient suffering for multiple myeloma R. Sans-Boza, E. Villamil Plymouth Hospitals NHS Trust, Neurophysiology, Plymouth, United Kingdom Case report of a 59 year old in treatment for multiple myeloma, that suffered a severe herpes zoster infection in the left brachial plexus territory. 3 weeks after symptoms onset he developed severe weakness of muscles in the shoulder girdle as well as sesnory symptoms like paresthesiae in both hands and forearms. NCS and EMG examination was undertaken. Nerve conduction tests showed increased distal motor and sensory latencies in the median nerves. There was no reproducible motor response from biceps when stimulating the left musculocutaneous nerve, and the response from Deltoid when stimualting the left axillary nerve was very low in amplitude. The contralateral motor responses were normal. EMG showed a severe pattern of acute dennervation without volitional activity in the left biceps brachii muscle. Left Deltoid and Infraspinatus showed also signs of acute dennervation but some volitional activity was preserved. Left Upper Trapezius, Triceps and pronator teres showed largely normal EMG features. After extensive questioning the patient admitted to sensory symptoms in his hands prior to the herpetic infection. However, there were no other…

Neurology, 2004

The clinical and neurophysiologic data from 65 patients taking thalidomide were reviewed. Thalido... more The clinical and neurophysiologic data from 65 patients taking thalidomide were reviewed. Thalidomide sensory neurotoxicity was found to be cumulative dose dependent but occurs only when the total dose is relatively high (&gt;20 g). The risk of developing sensory neuropathy is around 10% below this threshold but increases with higher doses.

European Spine Journal, 2015

PurposeCombined intraoperative monitoring (IOM) of transcranial electric motor-evoked potentials ... more PurposeCombined intraoperative monitoring (IOM) of transcranial electric motor-evoked potentials (tce-MEPs) and somatosensory-evoked potentials (SSEPs) is safe and effective for spinal cord monitoring during scoliosis surgery. However, the literature data regarding the reliability of spinal cord monitoring in patients with neuromuscular scoliosis are conflicting and need to be confirmed.MethodsWe reviewed IOM records of 40 consecutive patients with neuromuscular scoliosis related to central nervous system (CNS) (29 pts) or peripheral nervous system (PNS) (11 patients) diseases, who underwent posterior fusion with instrumentation surgery for spinal deformity. Multimodalitary IOM with SSEPs and tce-MEPs was performed.ResultsSpinal cord monitoring using at least one modality was attempted in 38/40 (95 %) patients. No false-negative results were present in either group, but a relatively high incidence of false-positive cases (4/29, 13.8 %) was noted in the CNS group. Two patients in the CNS group and one patient in the PNS group presented transient postoperative motor deficits (true positive), related to surgical manoeuvres in two cases and to malposition in the other one.ConclusionsMultimodalitary IOM is safe and effective to detect impending spinal cord and peripheral nerves dysfunction in neuromuscular scoliosis surgery. However, the interpretation of neurophysiological data may be challenging in such patients, and the rate of false-positive results is high when pre-operatory motor deficits are severe.

Journal of Neurology

Background Assessing the safety of SARS-CoV-2 mRNA vaccines and the effect of immunotherapies on ... more Background Assessing the safety of SARS-CoV-2 mRNA vaccines and the effect of immunotherapies on the seroconversion rate in patients with autoimmune neurological conditions (ANC) is relevant to clinical practice. Our aim was to assess the antibody response to and safety of SARS-CoV-2 mRNA vaccines in ANC. Methods This longitudinal study included ANC patients vaccinated with two doses of BNT162b2 or mRNA-1273 between March and August 2021. Side effects were assessed 2-10 days after each dose. Neurological status and anti-spike receptor binding domain antibody levels were evaluated before vaccination and 4 weeks after the second dose. Healthcare-workers served as controls for antibody levels. Results We included 300 ANC patients (median age 52, IQR 40-65), and 347 healthcare-workers (median age 45, IQR 34-54). mRNA-1273 vaccine was associated with an increased risk of both local (OR 2.52 95% CI 1.45-4.39, p = 0.001) and systemic reactions (OR 2.51% CI 1.49-4.23, p = 0.001). The incidence of relapse was not different before and after vaccine (Incidence rate ratio 0.72, 95% CI 0.29-1.83). Anti-SARS-CoV-2 IgG were detected in 268 (89.9%) patients and in all controls (p < 0.0001). BNT162b2 vaccine (OR 8.84 95% CI 2.32-33.65, p = 0.001), anti-CD20 mAb (OR 0.004 95% CI 0.0007-0.026, p < 0.0001) and fingolimod (OR 0.036 95% CI 0.002-0.628, p = 0•023) were associated with an increased risk of not developing anti-SARS-CoV-2 IgG. Conclusion SARS-CoV-2 mRNA vaccines were safe in a large group of ANC patients. Anti-CD20 and fingolimod treatment, as well as vaccination with the BNT162b2 vaccine, led to a reduced humoral response. These findings could inform vaccine policies in ANC patients undergoing immunotherapy.

Neurology, 2014

OBJECTIVE To describe the clinical and neurophysiological spectrum of neurotoxic peripheral motor... more OBJECTIVE To describe the clinical and neurophysiological spectrum of neurotoxic peripheral motor involvement in patients treated with Brentuximab Vedotin. BACKGROUND Brentuximab Vedotin is an antibody-drug conjugate composed by the anti-CD30 chimeric IgG1 monoclonal antibody cAC10 and the antimicrotubule drug monomethyllauristatin E. Brentuximab vedotin is effective as a single-agent therapy for the treatment of relapsed or refractory CD30-positive malignancies such as classical Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). Peripheral sensory neuropathy, grade 1 or 2 in severity, seems to be one of the most frequent adverse events. Grade 3 motor neuropathy is believed to be present only in a minority of patients. Discontinuation of treatment may be followed by improvement of the neurologic symptoms, but complete regression of the neuropathy is not the rule. CASE REPORTS We studied 7 patients treated with Brentuximab Vedotin for HL who developed a sensory-motor ne...

Neurology, 2014

BACKGROUND IncobotulinumtoxinA (Xeomin ®), a botulinum toxin type A drug without complexing prote... more BACKGROUND IncobotulinumtoxinA (Xeomin ®), a botulinum toxin type A drug without complexing proteins, became available in 2005. To our knowledge, this is the first randomized controlled double blind trial comparing the therapeutic effect of two non-bioequivalent toxins: IncobotulinumtoxinA and AbobotulinumtoxinA (Dysport ®) for treatment of primary axillary hyperhidrosis. METHODS: Twenty patients with primary axillary hyperhidrosis were treated with IncobotulinumtoxinA injections into one axilla and AbobotulinumtoxinA injections into the other axilla. Both patients and the physician were blinded as to which axilla received which of the two toxins. IncobotulinumtoxinA, 100 IU, and AbobotulinumtoxinA, 500IU, were diluted in 5 mL of 0.9% saline each. A total of 50 IU of IncobotulinumtoxinA or 250IU of AbobotulinumtoxinA was injected. Pain at the injection site has been evaluated by the VAS scale. A twelve month follow up is scheduled to evaluate the difference between these two toxins ...

European Journal of Cancer, 2013

Chemotherapy-induced peripheral neuropathy (CIPN) is a common neurological side-effect of cancer ... more Chemotherapy-induced peripheral neuropathy (CIPN) is a common neurological side-effect of cancer treatment and may lead to declines in patients' daily functioning and quality of life. To date, there are no modern clinimetrically well-evaluated outcome measures available to assess disability in CIPN patients. The objective of the study was to develop an interval-weighted scale to capture activity limitations and participation restrictions in CIPN patients using the Rasch methodology and to determine its validity and reliability properties. A preliminary Rasch-built Overall Disability Scale (pre-RODS) comprising 146 items was assessed twice (interval: 2-3 weeks; test-retest reliability) in 281 CIPN patients with a stable clinical condition. The obtained data were subjected to Rasch analyses to determine whether model expectations would be met, and if necessarily, adaptations were made to obtain proper model fit (internal validity). External validity was obtained by correlating the CIPN-RODS with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) neuropathy scales and the Pain-Intensity Numeric-Rating-Scale (PI-NRS). The preliminary RODS did not meet Rasch model's expectations. Items displaying misfit statistics, disordered thresholds, item bias or local dependency were systematically removed. The final CIPN-RODS consisting of 28 items fulfilled all the model's expectations with proper validity and reliability, and was unidimensional. The final CIPN-RODS is a Rasch-built disease-specific, interval measure suitable to detect disability in CIPN patients and bypasses the shortcomings of classical test theory ordinalbased measures. Its use is recommended in future clinical trials in CIPN.

Annals of Neurology, 2005

based on a thorough search of the medical literature and a poison control center consultation. Ta... more based on a thorough search of the medical literature and a poison control center consultation. Tamoxifen infrequently causes reversible neurotoxicity, but only at much higher doses (Ն160mg/m 2 daily). 5 Recent investigations into the use of artemisinin compounds in cancer treatment 6 have not been substantiated in clinical trials. Because of pervasive reports of animal brainstem toxicity, and the gradual emergence of similar patient cases, it becomes imperative to ascertain the safety of prolonged courses of artemisinin for cancer prophylaxis.

Amyloid, 2021

Abstract Background Ile68Leu transthyretin-related amyloidosis (ATTR) is known as a mainly or exc... more Abstract Background Ile68Leu transthyretin-related amyloidosis (ATTR) is known as a mainly or exclusively cardiogenic variant. We hypothesized that an accurate specialized neurological evaluation could reveal a consistent frequency of mixed phenotypes. Methods Forty-six consecutive subjects with transthyretin (TTR) Ile68Leu (p.Ile88Leu) mutation (29 patients and 17 unaffected carriers) underwent an in-depth cardiac and neurologic evaluation at a single center. Results All 29 patients showed cardiac involvement. In 20 (69%) cases, it was associated with neurological abnormalities (i.e. a mixed phenotype): 10 (35% of the total) had signs and symptoms of neuropathy, 5 (17%) had abnormalities at the neurologic specialist examination but without symptoms, and 5 (17%) had abnormal nerve conduction study only. None of the asymptomatic carriers showed neurological abnormalities or cardiac involvement. The Neuropathy Impairment Score was > 5 in seven patients at baseline, and became >5 in six more patients during follow-up. The probability of experiencing a major adverse cardiac event (MACE) during follow-up was higher in the mixed than cardiologic phenotype (p = 0.026). Age and phenotype were independent prognostic predictors of MACE. Conclusion At least two-thirds of patients with Ile68Leu ATTR and amyloidotic cardiomyopathy show an associated – definite or probable – neurologic impairment of variable degree if accurately evaluated in a neurologic setting. This proportion can rise during follow-up. The mixed phenotype carries a worse prognosis compared to the exclusively cardiologic one. These observations show that more patients could be eligible for treatment with gene silencers than currently indicated and highlight the need for an in-depth and continuous multidisciplinary evaluation of Ile68Leu ATTR patients.