Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a subtype of stiff-person syn... more Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a subtype of stiff-person syndrome (formerly stiff-man syndrome). It is rare and disabling, and characterised by brainstem symptoms, muscle stiffness, breathing issues and autonomic dysfunction. We describe a 65-year-old man who presented with odynophagia together with tongue and neck swelling, followed by multiple cranial nerve palsies culminating in bilateral vocal cord paralysis with acute stridor. He subsequently developed progressive generalised hypertonia and painful limb spasms. Serum antiglycine receptor antibody was strongly positive, but antiglutamic acid decarboxylase and other antibodies relating to stiff-person syndrome were negative. We diagnosed PERM and gave intravenous corticosteroids and immunoglobulins without benefit; however, following plasma exchange he has made a sustained improvement.
Journal of Neurology, Neurosurgery, and Psychiatry, Feb 9, 2012
Published cases of post-malaria neurological syndrome (PMNS) invariably report clinical and radio... more Published cases of post-malaria neurological syndrome (PMNS) invariably report clinical and radiological encephalopathy. We report a case of brainstem and spinal cord inflammation without supratentorial involvement following recovery from Plasmodium falciparum infection. A 48-year-old woman was diagnosed with P falciparum malaria while on holiday in Sierra Leone, during which she did not take malaria prophylaxis. She responded well to artesunate and amiodaquine. Ten days later, back in the UK, she was admitted to hospital with progressive sensorimotor symptoms in both legs and urinary retention. Neurological examination revealed upbeat nystagmus, minimal neck and shoulder muscle weakness (MRC 4+/5) with hyperreflexia, flaccid paraplegia with retained reflexes, reduced anal tone and a sensory level at T3/4. MRI of the neuraxis showed high signal in the pons, cerebellar peduncles, medulla and most of the spinal cord. The rest of the brain parenchyma was normal. Lumbar puncture was omitted due to brainstem swelling. An extensive infective and autoimmune screen, including aquaporin-4 antibodies, was normal. The patient received 3 days of IV methylprednisolone. Toe movement returned within 36 h and she had minimal paraparesis by 2 weeks. A repeat MRI after 3 weeks showed improvement in signal change with resolution of brainstem swelling. It is argued that the recognised clinical spectrum of PMNS should be expanded to include brainstem and/or spinal cord involvement.
Amyloidoma is a rare cause for intracranial space-occupying lesions diagnosed on brain imaging. H... more Amyloidoma is a rare cause for intracranial space-occupying lesions diagnosed on brain imaging. Histology of excised tissue usually reveals the presence of a discrete, λ-light chain secreting plasmacytoma adjacent to an amyloid mass comprising aggregated monoclonal immunoglobulin light chains. We described a patient with intracerebral amyloidoma associated with a localised lymphoplasmacytic lymphoma and no systemic paraproteinaemia, tumour or amyloid deposits.
Journal of Neurology, Neurosurgery & Psychiatry, 2012
Mitotic errors during early embryonal cell cleavage result in somatic cells having different geno... more Mitotic errors during early embryonal cell cleavage result in somatic cells having different genotypes. Such somatic mosaicism, in the presence of a chromosomal or genetic disorder, generally results in a milder disease phenotype, which may go undetected. We describe a case of mosaic tuberous sclerosis (TS) and the circumstances leading to its diagnosis. A 39-year-old man was referred to the adult neurology services for episodes of facial flushing, lip smacking, gustatory hallucinations and clenching movements of his left hand. EEG captured a complex partial seizure with correlating rhythmic θ activity over the right fronto-temporal area. MRI brain in 2004 showed a single high signal area in the right temporal lobe that was deemed artefactual. He was started on levetiracetam and later carbamazepine and was added, with good control. In 2009, his twin children were both diagnosed with tuberous sclerosis caused by a TSC2 exon 9 deletion. Neither the patient nor his wife carried the deletion in blood DNA. To investigate the possibility of somatic mosaicism, both parents underwent renal ultrasound. The patient's ultrasound revealed multiple hyperechoic foci throughout both kidneys typical in appearance of angiomyolipomas. Repeat MRI in 2010 showed disseminated lesions in both hemispheres, suggestive of cortical dysplasia that had emerged in the intervening 6 years. He was diagnosed with mosaic TS, and continues to be regularly reviewed for his epilepsy and renal lesions.
Journal of Neurology, Neurosurgery & Psychiatry, 2012
We report a case of paraneoplastic limbic encephalitis presenting with purely olfactory symptoms.... more We report a case of paraneoplastic limbic encephalitis presenting with purely olfactory symptoms. For 7 weeks, a 76-year-old man experienced distorted impressions of the odour of most foods and liquids and hallucinatory olfactory perceptions without objective stimuli. The perceived odour was metallic and foul, causing loss of appetite and weight, nausea and repeated retching. No dental or ENT cause for his symptoms was found. MRI of the brain and sinuses was normal. EEG showed no focal or paroxysmal activity. CSF protein was elevated (1.17 g) and isoelectric focusing revealed oligoclonal bands (3+) in the CSF only. A paraneoplastic antibody screen was positive for anti-Hu and weakly positive for anti-amphiphysin. CT TAP revealed malignant-appearing mediastinal lymphadenopathy but no pulmonary abnormality. The patient underwent endoscopic biopsy of the enlarged subcarinal lymph nodes. Histology confirmed metastatic small cell lung carcinoma (SCLC). Clinically, he was initially intact but later developed diplopia and bilateral horizontal nystagmus on lateral gaze. His gait became ataxic, veering towards the left, and he developed asymmetrical leg weakness, L>R. Repeat MRI brain and spine showed no metastatic deposits to explain his symptoms. Olfactory abnormalities may be associated with limbic encephalitis but have never been reported as an isolated presenting symptom. Occult malignancy should be considered in new onset olfactory symptoms in the absence of other causes.
Tremor is defined as an involuntary, oscillatory, rhythmic movement of a body part produced by th... more Tremor is defined as an involuntary, oscillatory, rhythmic movement of a body part produced by the alternating contractions of antagonistic pairs or muscles. It is the most common movement abnormality encountered and investigated in both primary care and neurology practice. Tremor is not a diagnosis in itself; rather it is symptomatic of an underlying disorder that should be identified and when possible treated. The diagnostic process ought to include a detailed medical history, a careful assessment of the characteristics of the tremor and a search for other neurological or physical signs. This process may present challenges, particularly in describing tremor phenomenology and linking it to the likely diagnosis. This article outlines briefly the main points to explore when evaluating a patient’s tremor history, the key characteristics of tremor that should be examined for and the correct nomenclature for their description, followed by an overview of the common types of tremor encoun...
Journal of Neurology, Neurosurgery, and Psychiatry, 2019
Background Alemtuzumab, a CD52 - specific monoclonal antibody depletes T and B cell population to... more Background Alemtuzumab, a CD52 - specific monoclonal antibody depletes T and B cell population to reduce relapse in multiple sclerosis. Neutrophils also express low levels of CD52 and can be depleted transiently by alemtuzumab, increasing the risk of infection in the post-alemtuzumab treatment period. Aim In this study in the Greater Manchester Neuroscience Centre (GMNC) we investigated at risk population for alemtuzumab induced neutropaenia. The outcome of these patients is also discussed. Method Retrospective study of patients who developed neutropaenia following treatment with alemtuzumab at the GMNC. Data of patient demographics, grade of neutropeania, symptoms while neutropaenic and management were evaluated. Results Of the 131 patient (86 F: 45 M) treated with alemtuzumab (1.9 F: 1 M ratio), 18 patient (13.7%) developed neutropaenia (17 F Vs 1 M, 19.8% F Vs 2.2% M). Moderate to severe (grade 2–4) neutropaenia was only observed in females. Average duration to develop neutropaen...
Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a subtype of stiff-person syn... more Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a subtype of stiff-person syndrome (formerly stiff-man syndrome). It is rare and disabling, and characterised by brainstem symptoms, muscle stiffness, breathing issues and autonomic dysfunction. We describe a 65-year-old man who presented with odynophagia together with tongue and neck swelling, followed by multiple cranial nerve palsies culminating in bilateral vocal cord paralysis with acute stridor. He subsequently developed progressive generalised hypertonia and painful limb spasms. Serum antiglycine receptor antibody was strongly positive, but antiglutamic acid decarboxylase and other antibodies relating to stiff-person syndrome were negative. We diagnosed PERM and gave intravenous corticosteroids and immunoglobulins without benefit; however, following plasma exchange he has made a sustained improvement.
Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a subtype of stiff-person syn... more Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a subtype of stiff-person syndrome (formerly stiff-man syndrome). It is rare and disabling, and characterised by brainstem symptoms, muscle stiffness, breathing issues and autonomic dysfunction. We describe a 65-year-old man who presented with odynophagia together with tongue and neck swelling, followed by multiple cranial nerve palsies culminating in bilateral vocal cord paralysis with acute stridor. He subsequently developed progressive generalised hypertonia and painful limb spasms. Serum antiglycine receptor antibody was strongly positive, but antiglutamic acid decarboxylase and other antibodies relating to stiff-person syndrome were negative. We diagnosed PERM and gave intravenous corticosteroids and immunoglobulins without benefit; however, following plasma exchange he has made a sustained improvement.
Journal of Neurology, Neurosurgery, and Psychiatry, 2017
In 2014, teriflunomide and dimethyl fumarate were approved by NHS regulators as first-line oral t... more In 2014, teriflunomide and dimethyl fumarate were approved by NHS regulators as first-line oral treatments for multiple sclerosis in England. We audited the safety, tolerability and treatment retention rates of the first line oral DMTs in Greater Manchester. Case notes of MS patients treated with first line oral DMTs were analysed for drug discontinuation reason, blood monitoring compliance and drug related side effects within the first 12 months of treatment. Of 39 patients, treated with teriflunomide, 89% were still on treatment at 12 months and reported very few side effects. 5% withdrew from treatment due to non-adherence with blood test monitoring, 3% due to lack of efficacy and 3% due to side effects. 273 patients treated with dimethyl fumarate, had a retention rate of 75% after 12 months. 12% discontinued treatment due to gastrointestinal side effects and 3% due to fatigue, headache and depression. Occasionally patients reported appetite/weight changes and altered hair appear...
Amyotrophic lateral sclerosis (ALS) is frequently caused by mutations in the SOD1 gene. Here, we ... more Amyotrophic lateral sclerosis (ALS) is frequently caused by mutations in the SOD1 gene. Here, we report the first SOD1 variant in Malta, an archipelago of three inhabited islands in southern Europe. We describe a patient with a sporadic form of ALS living on the island of Gozo in which the heterozygous SOD1 c.272A>C; p.(Asp91Ala) variant was detected. The patient had a late onset (79 years), sensory impairments and rapid disease progression culminating in respiratory failure. ALS has not yet developed in any of the three additional family members in which the D91A variant was identified. None of the healthy controls from the Maltese population were found to carry this variant. This report underscores the high prevalence of the D91A variant in Europe, despite the presence of a North-South gradient in its frequency, and confirms that this variant can be associated with dominant cases in Mediterranean countries.
Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a subtype of stiff-person syn... more Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a subtype of stiff-person syndrome (formerly stiff-man syndrome). It is rare and disabling, and characterised by brainstem symptoms, muscle stiffness, breathing issues and autonomic dysfunction. We describe a 65-year-old man who presented with odynophagia together with tongue and neck swelling, followed by multiple cranial nerve palsies culminating in bilateral vocal cord paralysis with acute stridor. He subsequently developed progressive generalised hypertonia and painful limb spasms. Serum antiglycine receptor antibody was strongly positive, but antiglutamic acid decarboxylase and other antibodies relating to stiff-person syndrome were negative. We diagnosed PERM and gave intravenous corticosteroids and immunoglobulins without benefit; however, following plasma exchange he has made a sustained improvement.
Journal of Neurology, Neurosurgery, and Psychiatry, Feb 9, 2012
Published cases of post-malaria neurological syndrome (PMNS) invariably report clinical and radio... more Published cases of post-malaria neurological syndrome (PMNS) invariably report clinical and radiological encephalopathy. We report a case of brainstem and spinal cord inflammation without supratentorial involvement following recovery from Plasmodium falciparum infection. A 48-year-old woman was diagnosed with P falciparum malaria while on holiday in Sierra Leone, during which she did not take malaria prophylaxis. She responded well to artesunate and amiodaquine. Ten days later, back in the UK, she was admitted to hospital with progressive sensorimotor symptoms in both legs and urinary retention. Neurological examination revealed upbeat nystagmus, minimal neck and shoulder muscle weakness (MRC 4+/5) with hyperreflexia, flaccid paraplegia with retained reflexes, reduced anal tone and a sensory level at T3/4. MRI of the neuraxis showed high signal in the pons, cerebellar peduncles, medulla and most of the spinal cord. The rest of the brain parenchyma was normal. Lumbar puncture was omitted due to brainstem swelling. An extensive infective and autoimmune screen, including aquaporin-4 antibodies, was normal. The patient received 3 days of IV methylprednisolone. Toe movement returned within 36 h and she had minimal paraparesis by 2 weeks. A repeat MRI after 3 weeks showed improvement in signal change with resolution of brainstem swelling. It is argued that the recognised clinical spectrum of PMNS should be expanded to include brainstem and/or spinal cord involvement.
Amyloidoma is a rare cause for intracranial space-occupying lesions diagnosed on brain imaging. H... more Amyloidoma is a rare cause for intracranial space-occupying lesions diagnosed on brain imaging. Histology of excised tissue usually reveals the presence of a discrete, λ-light chain secreting plasmacytoma adjacent to an amyloid mass comprising aggregated monoclonal immunoglobulin light chains. We described a patient with intracerebral amyloidoma associated with a localised lymphoplasmacytic lymphoma and no systemic paraproteinaemia, tumour or amyloid deposits.
Journal of Neurology, Neurosurgery & Psychiatry, 2012
Mitotic errors during early embryonal cell cleavage result in somatic cells having different geno... more Mitotic errors during early embryonal cell cleavage result in somatic cells having different genotypes. Such somatic mosaicism, in the presence of a chromosomal or genetic disorder, generally results in a milder disease phenotype, which may go undetected. We describe a case of mosaic tuberous sclerosis (TS) and the circumstances leading to its diagnosis. A 39-year-old man was referred to the adult neurology services for episodes of facial flushing, lip smacking, gustatory hallucinations and clenching movements of his left hand. EEG captured a complex partial seizure with correlating rhythmic θ activity over the right fronto-temporal area. MRI brain in 2004 showed a single high signal area in the right temporal lobe that was deemed artefactual. He was started on levetiracetam and later carbamazepine and was added, with good control. In 2009, his twin children were both diagnosed with tuberous sclerosis caused by a TSC2 exon 9 deletion. Neither the patient nor his wife carried the deletion in blood DNA. To investigate the possibility of somatic mosaicism, both parents underwent renal ultrasound. The patient's ultrasound revealed multiple hyperechoic foci throughout both kidneys typical in appearance of angiomyolipomas. Repeat MRI in 2010 showed disseminated lesions in both hemispheres, suggestive of cortical dysplasia that had emerged in the intervening 6 years. He was diagnosed with mosaic TS, and continues to be regularly reviewed for his epilepsy and renal lesions.
Journal of Neurology, Neurosurgery & Psychiatry, 2012
We report a case of paraneoplastic limbic encephalitis presenting with purely olfactory symptoms.... more We report a case of paraneoplastic limbic encephalitis presenting with purely olfactory symptoms. For 7 weeks, a 76-year-old man experienced distorted impressions of the odour of most foods and liquids and hallucinatory olfactory perceptions without objective stimuli. The perceived odour was metallic and foul, causing loss of appetite and weight, nausea and repeated retching. No dental or ENT cause for his symptoms was found. MRI of the brain and sinuses was normal. EEG showed no focal or paroxysmal activity. CSF protein was elevated (1.17 g) and isoelectric focusing revealed oligoclonal bands (3+) in the CSF only. A paraneoplastic antibody screen was positive for anti-Hu and weakly positive for anti-amphiphysin. CT TAP revealed malignant-appearing mediastinal lymphadenopathy but no pulmonary abnormality. The patient underwent endoscopic biopsy of the enlarged subcarinal lymph nodes. Histology confirmed metastatic small cell lung carcinoma (SCLC). Clinically, he was initially intact but later developed diplopia and bilateral horizontal nystagmus on lateral gaze. His gait became ataxic, veering towards the left, and he developed asymmetrical leg weakness, L>R. Repeat MRI brain and spine showed no metastatic deposits to explain his symptoms. Olfactory abnormalities may be associated with limbic encephalitis but have never been reported as an isolated presenting symptom. Occult malignancy should be considered in new onset olfactory symptoms in the absence of other causes.
Tremor is defined as an involuntary, oscillatory, rhythmic movement of a body part produced by th... more Tremor is defined as an involuntary, oscillatory, rhythmic movement of a body part produced by the alternating contractions of antagonistic pairs or muscles. It is the most common movement abnormality encountered and investigated in both primary care and neurology practice. Tremor is not a diagnosis in itself; rather it is symptomatic of an underlying disorder that should be identified and when possible treated. The diagnostic process ought to include a detailed medical history, a careful assessment of the characteristics of the tremor and a search for other neurological or physical signs. This process may present challenges, particularly in describing tremor phenomenology and linking it to the likely diagnosis. This article outlines briefly the main points to explore when evaluating a patient’s tremor history, the key characteristics of tremor that should be examined for and the correct nomenclature for their description, followed by an overview of the common types of tremor encoun...
Journal of Neurology, Neurosurgery, and Psychiatry, 2019
Background Alemtuzumab, a CD52 - specific monoclonal antibody depletes T and B cell population to... more Background Alemtuzumab, a CD52 - specific monoclonal antibody depletes T and B cell population to reduce relapse in multiple sclerosis. Neutrophils also express low levels of CD52 and can be depleted transiently by alemtuzumab, increasing the risk of infection in the post-alemtuzumab treatment period. Aim In this study in the Greater Manchester Neuroscience Centre (GMNC) we investigated at risk population for alemtuzumab induced neutropaenia. The outcome of these patients is also discussed. Method Retrospective study of patients who developed neutropaenia following treatment with alemtuzumab at the GMNC. Data of patient demographics, grade of neutropeania, symptoms while neutropaenic and management were evaluated. Results Of the 131 patient (86 F: 45 M) treated with alemtuzumab (1.9 F: 1 M ratio), 18 patient (13.7%) developed neutropaenia (17 F Vs 1 M, 19.8% F Vs 2.2% M). Moderate to severe (grade 2–4) neutropaenia was only observed in females. Average duration to develop neutropaen...
Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a subtype of stiff-person syn... more Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a subtype of stiff-person syndrome (formerly stiff-man syndrome). It is rare and disabling, and characterised by brainstem symptoms, muscle stiffness, breathing issues and autonomic dysfunction. We describe a 65-year-old man who presented with odynophagia together with tongue and neck swelling, followed by multiple cranial nerve palsies culminating in bilateral vocal cord paralysis with acute stridor. He subsequently developed progressive generalised hypertonia and painful limb spasms. Serum antiglycine receptor antibody was strongly positive, but antiglutamic acid decarboxylase and other antibodies relating to stiff-person syndrome were negative. We diagnosed PERM and gave intravenous corticosteroids and immunoglobulins without benefit; however, following plasma exchange he has made a sustained improvement.
Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a subtype of stiff-person syn... more Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a subtype of stiff-person syndrome (formerly stiff-man syndrome). It is rare and disabling, and characterised by brainstem symptoms, muscle stiffness, breathing issues and autonomic dysfunction. We describe a 65-year-old man who presented with odynophagia together with tongue and neck swelling, followed by multiple cranial nerve palsies culminating in bilateral vocal cord paralysis with acute stridor. He subsequently developed progressive generalised hypertonia and painful limb spasms. Serum antiglycine receptor antibody was strongly positive, but antiglutamic acid decarboxylase and other antibodies relating to stiff-person syndrome were negative. We diagnosed PERM and gave intravenous corticosteroids and immunoglobulins without benefit; however, following plasma exchange he has made a sustained improvement.
Journal of Neurology, Neurosurgery, and Psychiatry, 2017
In 2014, teriflunomide and dimethyl fumarate were approved by NHS regulators as first-line oral t... more In 2014, teriflunomide and dimethyl fumarate were approved by NHS regulators as first-line oral treatments for multiple sclerosis in England. We audited the safety, tolerability and treatment retention rates of the first line oral DMTs in Greater Manchester. Case notes of MS patients treated with first line oral DMTs were analysed for drug discontinuation reason, blood monitoring compliance and drug related side effects within the first 12 months of treatment. Of 39 patients, treated with teriflunomide, 89% were still on treatment at 12 months and reported very few side effects. 5% withdrew from treatment due to non-adherence with blood test monitoring, 3% due to lack of efficacy and 3% due to side effects. 273 patients treated with dimethyl fumarate, had a retention rate of 75% after 12 months. 12% discontinued treatment due to gastrointestinal side effects and 3% due to fatigue, headache and depression. Occasionally patients reported appetite/weight changes and altered hair appear...
Amyotrophic lateral sclerosis (ALS) is frequently caused by mutations in the SOD1 gene. Here, we ... more Amyotrophic lateral sclerosis (ALS) is frequently caused by mutations in the SOD1 gene. Here, we report the first SOD1 variant in Malta, an archipelago of three inhabited islands in southern Europe. We describe a patient with a sporadic form of ALS living on the island of Gozo in which the heterozygous SOD1 c.272A>C; p.(Asp91Ala) variant was detected. The patient had a late onset (79 years), sensory impairments and rapid disease progression culminating in respiratory failure. ALS has not yet developed in any of the three additional family members in which the D91A variant was identified. None of the healthy controls from the Maltese population were found to carry this variant. This report underscores the high prevalence of the D91A variant in Europe, despite the presence of a North-South gradient in its frequency, and confirms that this variant can be associated with dominant cases in Mediterranean countries.
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Papers by Adrian Pace