Two groups of researchers independently described KMT2B gene mutations causing childhood-onset dy... more Two groups of researchers independently described KMT2B gene mutations causing childhood-onset dystonia in 2016. KMT2B-dystonia usually presents in the first decade of life with lower limb symptoms that progressively generalize. Patients have varying intellectual disability, dysphonia, and facial dysmorphism. Our proband is a 41-year-old male who presented with a decade of hand tremors, 2 years of head bobbing, and normal childhood gross motor development. Examination revealed head rotation and tilt to the right, severe hypertrophy in sternocleidomastoid and trapezii muscles, but no dysphonia or abnormal facial features. Severe neck retro-flexion and arching of the back made ambulation difficult (Video S1). Burke-Fahn-Marsden Movement and Disability Subscales (BFMMS, BFMDS) were 35 and 4, respectively. Intellectual function was at the 1st percentile (score 63, Wechsler Adult Intelligence Scale, 4th edition). Magnetic Resonance Imaging (MRI) of the brain was unremarkable. Anticholinergics, benzodiazepines, muscle-relaxants, and botulinum toxin were only partially effective. The patient’s mother had right hand dystonia and postural tremor (Video S1). Next-generation sequencing and copy number analysis revealed missense mutation (NM_014727.2: c.4960T>C (p.Cys1654Arg) in KMT2B in both the proband and mother. Other monogenic causes of dystonia were excluded (Supporting information in Appendix S1). The patient underwent bilateral GPi directional electrode implantation with robotic assistance (ROSA). Surgery was performed awake with a CRW frame and co-registration of preoperative 3.0 Tesla MRI and intraoperative CT scan. There were no untoward stimulation effects with microelectrodes from 15 mm above target, and final electrodes were implanted in the bilateral ventral posterolateral GPi, then confirmed by post-operative CT. His clinical effect was rapid (several days, see Video S1), with initial stimulation parameters of 2.5 milliamp, 120 microsecond pulse width at 130 Hertz (right lead contacts E10-11-12, left lead contacts E2-3-4). One month after initial programming, BFMMS and BFMDS scores were 4 and 1, respectively. Preoperative medications were ceased. Our proband’s dystonia started in his upper extremity in his late 20’s and worsened to involve the neck and trunk. KMT2Brelated dystonia typically starts in childhood with lower limb involvement, then generalizes. Involvement of the larynx and oromandibular region is nearly universal. Almost 80% of KMT2B-related dystonia patients have generalized dystonia. Dystonic hand tremor as the only manifestation of KMT2Brelated dystonia in his mother is extremely rare. Almost 30%– 50% of cases can have non-motor abnormalities such as dysmorphism, intellectual or developmental disability, short stature, microcephaly, dysphonia, or deafness. Our index case had intellectual disability, but no other non-motor manifestations. Only one other family has been described with KMT2Brelated dystonia due to this exact mutation. PolyPhen and SIFT analysis predict this variant’s pathogenicity. This allele is not found in the gnomAD database. Generally, older age at surgery is associated with worse outcomes in dystonia, as in Torsin-1 related dystonia (DYT-TOR1A). With a handful of cases reported, KMT2B-related disease seems to respond well to surgery despite older age. Improvement in the BFMMS score in our patient post-DBS was comparable to that of DYT-TOR1A. GPi DBS in DYT-SGCE, DYT-ACTB, DYT-TAF1, and DYT-GNAO1 have yielded results comparable to that of DYTTOR1A, whereas outcomes were worse in DYT-THAP1, DYT-PANK2, and DYT-ADCY-5.
Cephalalgia : an international journal of headache, Jan 9, 2016
The neuropeptide calcitonin gene-related peptide (CGRP) has now been established as a key player ... more The neuropeptide calcitonin gene-related peptide (CGRP) has now been established as a key player in migraine. However, the mechanisms underlying the reported elevation of CGRP in the serum and cerebrospinal fluid of some migraineurs are not known. A candidate mechanism is cortical spreading depression (CSD), which is associated with migraine with aura and traumatic brain injury. The aim of this study was to investigate whether CGRP gene expression may be induced by experimental CSD in the rat cerebral cortex. CSD was induced by topical application of KCl and monitored using electrophysiological methods. Quantitative PCR and ELISA were used to measure CGRP mRNA and peptide levels in discrete ipsilateral and contralateral cortical regions of the rat brain 24 hours following CSD events and compared with sham treatments. The data show that multiple, but not single, CSD events significantly increase CGRP mRNA levels at 24 hours post-CSD in the ipsilateral rat cerebral cortex. Increased C...
niospinal irradiation and chemotherapy presented with 2.5 weeks of progressive gait ataxia and he... more niospinal irradiation and chemotherapy presented with 2.5 weeks of progressive gait ataxia and headache. Patient was alert and oriented. The right pupil was sluggish. The left pupil was reactive and the left eye deviated uncontrollably on exam. The left upper extremity had 4/5 strength. CT scan showed an anterior septum pellucidum mass at the foramen of Monro with secondary obstructive hydrocephalus (Fig. ).
We present a 64-year-old woman who was evaluated after being found unresponsive. Imaging revealed... more We present a 64-year-old woman who was evaluated after being found unresponsive. Imaging revealed a foramen of Monro cavernoma resulting in hydrocephalus. Supratentorial cavernomas are most frequently found in the cerebral cortex, and although ventricular cavernomas do occur, they are rarely located in the foramen of Monro. Foramen of Monro cavernomas are extremely dangerous, requiring aggressive management when identified.
OBJECTIVE Craniectomy is often performed to decrease intracranial pressure following trauma and v... more OBJECTIVE Craniectomy is often performed to decrease intracranial pressure following trauma and vascular injuries. The subsequent cranioplasty procedures may be complicated by surgical site infections (SSIs) due to prior trauma, foreign implants, and multiple surgeries through a common incision. Several studies have found that intrawound vancomycin powder (VP) is associated with decreased risk of SSIs after spine operations. However, no previously published study has evaluated the effectiveness of VP in cranioplasty procedures. The purpose of this study was to determine whether intrawound VP is associated with decreased risk of SSIs, to evaluate VP's safety, and to identify risk factors for SSIs after cranioplasty among patients undergoing first-time cranioplasty. METHODS The authors conducted a retrospective cohort study of adult patients undergoing first-time cranioplasty for indications other than infections from January 1, 2008, to July 31, 2014, at an academic health center...
Lateral periodic discharges (LPDs) have been recognized as a common electroencephalographic (EEG)... more Lateral periodic discharges (LPDs) have been recognized as a common electroencephalographic (EEG) pattern in critically ill patients. However, management decisions in these patients are still a challenge for clinicians. This study investigates hemodynamic changes associated with LPDs and evaluates if this pattern is likely to represent an ictal, interictal, or ictal–interictal continuum phenomenon via non-invasive near infra-red spectroscopy (NIRS) with concurrent with continuous EEG. Seventeen patients admitted to the intensive care unit with LPDs on continuous electroencephalogram (EEG) were included. Participants engaged in NIRS recording—with scalp probes on right and left frontal regions simultaneously. Associations between LPDs laterality, primary frequency, NIRS a of cerebral oxygen saturation (SO2), total hemoglobin concentration (tHb), oxygenated hemoglobin concentration (O2Hb), de-oxygenated hemoglobin concentration (HHb), and variables in participant medical history were ...
ABBREVIATIONS ASA = American Society of Anesthesiologists; BMI = body mass index; IV = intravenou... more ABBREVIATIONS ASA = American Society of Anesthesiologists; BMI = body mass index; IV = intravenous; NHSN = National Healthcare Safety Network; OR = odds ratio; SSI = surgical site infection; VP = vancomycin powder. OBJECTIVE Craniectomy is often performed to decrease intracranial pressure following trauma and vascular injuries. The subsequent cranioplasty procedures may be complicated by surgical site infections (SSIs) due to prior trauma, foreign implants, and multiple surgeries through a common incision. Several studies have found that intrawound vanco-mycin powder (VP) is associated with decreased risk of SSIs after spine operations. However, no previously published study has evaluated the effectiveness of VP in cranioplasty procedures. The purpose of this study was to determine whether intrawound VP is associated with decreased risk of SSIs, to evaluate VP's safety, and to identify risk factors for SSIs after cranioplasty among patients undergoing first-time cranioplasty. METHODS The authors conducted a retrospective cohort study of adult patients undergoing first-time cranioplasty for indications other than infections from January 1, 2008, to July 31, 2014, at an academic health center. Data on de-mographics, possible risk factors for SSIs, and treatment with VP were collected from the patients' electronic health records. RESULTS During the study period, 258 patients underwent first-time cranioplasties, and 15 (5.8%) of these patients acquired SSIs. Ninety-two patients (35.7%) received intrawound VP (VP group) and 166 (64.3%) did not (no-VP group). Patients in the VP group and the no-VP group were similar with respect to age, sex, smoking history, body mass index, and SSI rates (VP group 6.5%, no-VP group 5.4%, p = 0.72). Patients in the VP group were less likely than those in the no-VP group to have undergone craniectomy for tumors and were more likely to have an American Society of Anes-thesiologists physical status score > 2. Intrawound VP was not associated with other postoperative complications. Risk factors for SSI from the bivariable analyses were diabetes (odds ratio [OR] 3.65, 95% CI 1.07–12.44), multiple crani-otomy procedures before the cranioplasty (OR 4.39, 95% CI 1.47–13.18), prior same-side craniotomy (OR 4.73, 95% CI 1.57–14.24), and prosthetic implants (OR 4.51, 95% CI 1.40–14.59). The multivariable analysis identified prior same-side craniotomy (OR 3.37, 95% CI 1.06–10.79) and prosthetic implants (OR 3.93, 95% CI 1.15–13.40) as significant risk factors for SSIs. After adjusting for potential confounders, patients with SSIs were more likely than those without SSIs to be readmitted (OR 7.28, 95% CI 2.07–25.60). CONCLUSIONS In this study, intrawound VP was not associated with a decreased risk of SSIs or with an increased risk of complications. Prior same-side craniotomy and prosthetic implants were risk factors for SSI after first-time cranio-plasty.
Medulloblastoma is a common pediatric tumor typically diagnosed before the age of fifteen. Initia... more Medulloblastoma is a common pediatric tumor typically diagnosed before the age of fifteen. Initial therapy includes surgical resection and radiation of the entire neuro-axis. Recurrence is common and typically occurs within 2 years of initial diagnosis. Those fitting Collin's Law is considered tumor-free. We report a case of single supratentorial recurrence 13 years after initial diagnosis. Here we present a 22 year old male presenting 13 years after initial diagnosis with isolated septum pellucidum recurrence. He underwent complete resection of the tumor. Medulloblastoma is a common in the pediatric population. Late recurrence to the ventricular system is uncommon. Long term follow-up is recommended in these patients.
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, Jan 24, 2015
We present a 23-year-old woman who was diagnosed with a malignant peripheral nerve sheath tumor (... more We present a 23-year-old woman who was diagnosed with a malignant peripheral nerve sheath tumor (MPNST), 17months following the resection of a schwannoma. MPNST is rare and is usually associated with neurofibromatosis. The typical treatment of resection and radiation is difficult to achieve in the spine.
We present a 64-year-old woman who was evaluated after being found unresponsive. Imaging revealed... more We present a 64-year-old woman who was evaluated after being found unresponsive. Imaging revealed a foramen of Monro cavernoma resulting in hydrocephalus. Supratentorial cavernomas are most frequently found in the cerebral cortex, and although ventricular cavernomas do occur, they are rarely located in the foramen of Monro. Foramen of Monro cavernomas are extremely dangerous, requiring aggressive management when identified.
Two groups of researchers independently described KMT2B gene mutations causing childhood-onset dy... more Two groups of researchers independently described KMT2B gene mutations causing childhood-onset dystonia in 2016. KMT2B-dystonia usually presents in the first decade of life with lower limb symptoms that progressively generalize. Patients have varying intellectual disability, dysphonia, and facial dysmorphism. Our proband is a 41-year-old male who presented with a decade of hand tremors, 2 years of head bobbing, and normal childhood gross motor development. Examination revealed head rotation and tilt to the right, severe hypertrophy in sternocleidomastoid and trapezii muscles, but no dysphonia or abnormal facial features. Severe neck retro-flexion and arching of the back made ambulation difficult (Video S1). Burke-Fahn-Marsden Movement and Disability Subscales (BFMMS, BFMDS) were 35 and 4, respectively. Intellectual function was at the 1st percentile (score 63, Wechsler Adult Intelligence Scale, 4th edition). Magnetic Resonance Imaging (MRI) of the brain was unremarkable. Anticholinergics, benzodiazepines, muscle-relaxants, and botulinum toxin were only partially effective. The patient’s mother had right hand dystonia and postural tremor (Video S1). Next-generation sequencing and copy number analysis revealed missense mutation (NM_014727.2: c.4960T>C (p.Cys1654Arg) in KMT2B in both the proband and mother. Other monogenic causes of dystonia were excluded (Supporting information in Appendix S1). The patient underwent bilateral GPi directional electrode implantation with robotic assistance (ROSA). Surgery was performed awake with a CRW frame and co-registration of preoperative 3.0 Tesla MRI and intraoperative CT scan. There were no untoward stimulation effects with microelectrodes from 15 mm above target, and final electrodes were implanted in the bilateral ventral posterolateral GPi, then confirmed by post-operative CT. His clinical effect was rapid (several days, see Video S1), with initial stimulation parameters of 2.5 milliamp, 120 microsecond pulse width at 130 Hertz (right lead contacts E10-11-12, left lead contacts E2-3-4). One month after initial programming, BFMMS and BFMDS scores were 4 and 1, respectively. Preoperative medications were ceased. Our proband’s dystonia started in his upper extremity in his late 20’s and worsened to involve the neck and trunk. KMT2Brelated dystonia typically starts in childhood with lower limb involvement, then generalizes. Involvement of the larynx and oromandibular region is nearly universal. Almost 80% of KMT2B-related dystonia patients have generalized dystonia. Dystonic hand tremor as the only manifestation of KMT2Brelated dystonia in his mother is extremely rare. Almost 30%– 50% of cases can have non-motor abnormalities such as dysmorphism, intellectual or developmental disability, short stature, microcephaly, dysphonia, or deafness. Our index case had intellectual disability, but no other non-motor manifestations. Only one other family has been described with KMT2Brelated dystonia due to this exact mutation. PolyPhen and SIFT analysis predict this variant’s pathogenicity. This allele is not found in the gnomAD database. Generally, older age at surgery is associated with worse outcomes in dystonia, as in Torsin-1 related dystonia (DYT-TOR1A). With a handful of cases reported, KMT2B-related disease seems to respond well to surgery despite older age. Improvement in the BFMMS score in our patient post-DBS was comparable to that of DYT-TOR1A. GPi DBS in DYT-SGCE, DYT-ACTB, DYT-TAF1, and DYT-GNAO1 have yielded results comparable to that of DYTTOR1A, whereas outcomes were worse in DYT-THAP1, DYT-PANK2, and DYT-ADCY-5.
Cephalalgia : an international journal of headache, Jan 9, 2016
The neuropeptide calcitonin gene-related peptide (CGRP) has now been established as a key player ... more The neuropeptide calcitonin gene-related peptide (CGRP) has now been established as a key player in migraine. However, the mechanisms underlying the reported elevation of CGRP in the serum and cerebrospinal fluid of some migraineurs are not known. A candidate mechanism is cortical spreading depression (CSD), which is associated with migraine with aura and traumatic brain injury. The aim of this study was to investigate whether CGRP gene expression may be induced by experimental CSD in the rat cerebral cortex. CSD was induced by topical application of KCl and monitored using electrophysiological methods. Quantitative PCR and ELISA were used to measure CGRP mRNA and peptide levels in discrete ipsilateral and contralateral cortical regions of the rat brain 24 hours following CSD events and compared with sham treatments. The data show that multiple, but not single, CSD events significantly increase CGRP mRNA levels at 24 hours post-CSD in the ipsilateral rat cerebral cortex. Increased C...
niospinal irradiation and chemotherapy presented with 2.5 weeks of progressive gait ataxia and he... more niospinal irradiation and chemotherapy presented with 2.5 weeks of progressive gait ataxia and headache. Patient was alert and oriented. The right pupil was sluggish. The left pupil was reactive and the left eye deviated uncontrollably on exam. The left upper extremity had 4/5 strength. CT scan showed an anterior septum pellucidum mass at the foramen of Monro with secondary obstructive hydrocephalus (Fig. ).
We present a 64-year-old woman who was evaluated after being found unresponsive. Imaging revealed... more We present a 64-year-old woman who was evaluated after being found unresponsive. Imaging revealed a foramen of Monro cavernoma resulting in hydrocephalus. Supratentorial cavernomas are most frequently found in the cerebral cortex, and although ventricular cavernomas do occur, they are rarely located in the foramen of Monro. Foramen of Monro cavernomas are extremely dangerous, requiring aggressive management when identified.
OBJECTIVE Craniectomy is often performed to decrease intracranial pressure following trauma and v... more OBJECTIVE Craniectomy is often performed to decrease intracranial pressure following trauma and vascular injuries. The subsequent cranioplasty procedures may be complicated by surgical site infections (SSIs) due to prior trauma, foreign implants, and multiple surgeries through a common incision. Several studies have found that intrawound vancomycin powder (VP) is associated with decreased risk of SSIs after spine operations. However, no previously published study has evaluated the effectiveness of VP in cranioplasty procedures. The purpose of this study was to determine whether intrawound VP is associated with decreased risk of SSIs, to evaluate VP's safety, and to identify risk factors for SSIs after cranioplasty among patients undergoing first-time cranioplasty. METHODS The authors conducted a retrospective cohort study of adult patients undergoing first-time cranioplasty for indications other than infections from January 1, 2008, to July 31, 2014, at an academic health center...
Lateral periodic discharges (LPDs) have been recognized as a common electroencephalographic (EEG)... more Lateral periodic discharges (LPDs) have been recognized as a common electroencephalographic (EEG) pattern in critically ill patients. However, management decisions in these patients are still a challenge for clinicians. This study investigates hemodynamic changes associated with LPDs and evaluates if this pattern is likely to represent an ictal, interictal, or ictal–interictal continuum phenomenon via non-invasive near infra-red spectroscopy (NIRS) with concurrent with continuous EEG. Seventeen patients admitted to the intensive care unit with LPDs on continuous electroencephalogram (EEG) were included. Participants engaged in NIRS recording—with scalp probes on right and left frontal regions simultaneously. Associations between LPDs laterality, primary frequency, NIRS a of cerebral oxygen saturation (SO2), total hemoglobin concentration (tHb), oxygenated hemoglobin concentration (O2Hb), de-oxygenated hemoglobin concentration (HHb), and variables in participant medical history were ...
ABBREVIATIONS ASA = American Society of Anesthesiologists; BMI = body mass index; IV = intravenou... more ABBREVIATIONS ASA = American Society of Anesthesiologists; BMI = body mass index; IV = intravenous; NHSN = National Healthcare Safety Network; OR = odds ratio; SSI = surgical site infection; VP = vancomycin powder. OBJECTIVE Craniectomy is often performed to decrease intracranial pressure following trauma and vascular injuries. The subsequent cranioplasty procedures may be complicated by surgical site infections (SSIs) due to prior trauma, foreign implants, and multiple surgeries through a common incision. Several studies have found that intrawound vanco-mycin powder (VP) is associated with decreased risk of SSIs after spine operations. However, no previously published study has evaluated the effectiveness of VP in cranioplasty procedures. The purpose of this study was to determine whether intrawound VP is associated with decreased risk of SSIs, to evaluate VP's safety, and to identify risk factors for SSIs after cranioplasty among patients undergoing first-time cranioplasty. METHODS The authors conducted a retrospective cohort study of adult patients undergoing first-time cranioplasty for indications other than infections from January 1, 2008, to July 31, 2014, at an academic health center. Data on de-mographics, possible risk factors for SSIs, and treatment with VP were collected from the patients' electronic health records. RESULTS During the study period, 258 patients underwent first-time cranioplasties, and 15 (5.8%) of these patients acquired SSIs. Ninety-two patients (35.7%) received intrawound VP (VP group) and 166 (64.3%) did not (no-VP group). Patients in the VP group and the no-VP group were similar with respect to age, sex, smoking history, body mass index, and SSI rates (VP group 6.5%, no-VP group 5.4%, p = 0.72). Patients in the VP group were less likely than those in the no-VP group to have undergone craniectomy for tumors and were more likely to have an American Society of Anes-thesiologists physical status score > 2. Intrawound VP was not associated with other postoperative complications. Risk factors for SSI from the bivariable analyses were diabetes (odds ratio [OR] 3.65, 95% CI 1.07–12.44), multiple crani-otomy procedures before the cranioplasty (OR 4.39, 95% CI 1.47–13.18), prior same-side craniotomy (OR 4.73, 95% CI 1.57–14.24), and prosthetic implants (OR 4.51, 95% CI 1.40–14.59). The multivariable analysis identified prior same-side craniotomy (OR 3.37, 95% CI 1.06–10.79) and prosthetic implants (OR 3.93, 95% CI 1.15–13.40) as significant risk factors for SSIs. After adjusting for potential confounders, patients with SSIs were more likely than those without SSIs to be readmitted (OR 7.28, 95% CI 2.07–25.60). CONCLUSIONS In this study, intrawound VP was not associated with a decreased risk of SSIs or with an increased risk of complications. Prior same-side craniotomy and prosthetic implants were risk factors for SSI after first-time cranio-plasty.
Medulloblastoma is a common pediatric tumor typically diagnosed before the age of fifteen. Initia... more Medulloblastoma is a common pediatric tumor typically diagnosed before the age of fifteen. Initial therapy includes surgical resection and radiation of the entire neuro-axis. Recurrence is common and typically occurs within 2 years of initial diagnosis. Those fitting Collin's Law is considered tumor-free. We report a case of single supratentorial recurrence 13 years after initial diagnosis. Here we present a 22 year old male presenting 13 years after initial diagnosis with isolated septum pellucidum recurrence. He underwent complete resection of the tumor. Medulloblastoma is a common in the pediatric population. Late recurrence to the ventricular system is uncommon. Long term follow-up is recommended in these patients.
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, Jan 24, 2015
We present a 23-year-old woman who was diagnosed with a malignant peripheral nerve sheath tumor (... more We present a 23-year-old woman who was diagnosed with a malignant peripheral nerve sheath tumor (MPNST), 17months following the resection of a schwannoma. MPNST is rare and is usually associated with neurofibromatosis. The typical treatment of resection and radiation is difficult to achieve in the spine.
We present a 64-year-old woman who was evaluated after being found unresponsive. Imaging revealed... more We present a 64-year-old woman who was evaluated after being found unresponsive. Imaging revealed a foramen of Monro cavernoma resulting in hydrocephalus. Supratentorial cavernomas are most frequently found in the cerebral cortex, and although ventricular cavernomas do occur, they are rarely located in the foramen of Monro. Foramen of Monro cavernomas are extremely dangerous, requiring aggressive management when identified.
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