Cerebellar Atrophy (MS)
Summary: While it is common, there is no reason not to look at vitamin B levels and possibly turmeric to oppose worsening. Also think about elevated alkaline phosphatase, acetyl-carnitine, and even L-dopa.
J Neurol. 2013 May;260(5):1358-66. doi: 10.1007/s00415-012-6805-y. Epub 2012 Dec 28.
MR imaging and cognitive correlates of relapsing-remitting multiple sclerosis patients with cerebellar symptoms.
Cerasa A, Valentino P, Chiriaco C, Pirritano D, Nisticò R, Gioia CM, Trotta M, Del Giudice F, Tallarico T, Rocca F, Augimeri A, Bilotti G, Quattrone A.
Neuroimaging Research Unit, Institute of Neurological Sciences, National Research Council, 88100, Germaneto, CZ, Italy. email@example.com
Multiple sclerosis (MS) is a demyelinating disease affecting the central nervous system, frequently associated with cognitive impairments. Damages of the cerebellum are very common features of patients with MS, although the impact of this clinical factor is generally neglected. Recent evidence from our group demonstrated that MS patients with cerebellar damages are characterized by selective cognitive dysfunctions related to attention and language abilities. Here, we aimed at investigating the presence of neuroanatomical abnormalities in relapsing-remitting MS patients with (RR-MSc) and without (RR-MSnc) cerebellar signs. Twelve RR-MSc patients, 14 demographically, clinically, and radiologically, matched RR-MSnc patients and 20 controls were investigated. All patients underwent neuropsychological assessment. After refilling of FLAIR lesions on the 3D T1-weighted images, VBM was performed using SPM8 and DARTEL. A correlation analysis was performed between VBM results and neuropsychological variables characterizing RR-MSc patients. Despite a similar clinical status, RR-MSc patients were characterized by more severe cognitive damages in attention and language domains with respect to RR-MSnc and controls. With respect to controls, RR-MSnc patients were characterized by a specific atrophy of the bilateral thalami that became more widespread (including motor cortex) in the RR-MSc group (FWE < 0.05). However, consistent with their well-defined neuropsychological deficits, RR-MSc group showed atrophies in the prefrontal and temporal cortical areas when directly compared with RR-MSnc group. Our results demonstrated that RR-MS patients having cerebellar signs were characterized by a distinct neuroanatomical profile, mainly involving cortical regions underpinning executive functions and verbal fluency.
Arch Neurol. 2012 Oct;69(10):1366-71. doi: 10.1001/archneurol.2012.2356.
Slowly progressive ataxia, neuropathy, and oculomotor dysfunction.
Jordan JT, Samuel G, Vernino S, Muppidi S.
Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Justin.Jordan@phhs.org
A 54-year-old white man presented with slowly progressive incoordination and weakness. He had normal motor development until, at 16 years of age, he noted difficulty walking and difficulty reading despite normal visual acuity. By the fourth decade of life, he developed poor coordination and balance, as well as inability to walk. In subsequent years, he developed progressive, painless sensory loss, weakness, and atrophy in his distal arms and legs. His vision problems progressed and he also developed dysarthria without dysphagia. Family history was negative except for an uncle who was described as "clumsy." Results of an oculomotor examination were notable for increased square-wave jerks, persistent bilateral gaze-evoked nystagmus with saccadic pursuit, intact vestibulo-ocular reflex, and saccadic dysmetria. He had a mixed dysarthria with flaccid and ataxic characteristics and severe weakness and atrophy in the distal limb muscles. Sensation was diminished to the midforearms and midthighs in all modalities. Deep tendon reflexes were absent throughout, with no response to plantar stimulation. He had marked appendicular ataxia with mild axial ataxia. Magnetic resonance imaging of the brain revealed severe cerebellar atrophy. Results of an electrodiagnostic study suggested a severe axonal sensorimotor polyneuropathy with active and chronic denervation. The differential diagnosis in a patient with ataxia, neuropathy, and oculomotor features is discussed; a methodical approach to the diagnostic workup is suggested; and the final diagnosis is revealed.
Child Adolesc Psychiatry Ment Health. 2012 Jun 22;6(1):25. doi: 10.1186/1753-2000-6-25.
Mood disorder with mixed, psychotic features due to vitamin b12 deficiency in an adolescent: case report.
Tufan AE, Bilici R, Usta G, Erdoğan A.
Assistant Professor, Abant Izzet Baysal University Medical Faculty, Department of Child and Adolescent Psychiatry, Baysal, Turkey. firstname.lastname@example.org.
Vitamin B12 is one of the essential vitamins affecting various systems of the body. Reports of psychiatric disorders due to its deficiency mostly focus on middle aged and elderly patients. Here we report a case of vitamin B 12 deficiency in a 16-year old, male adolescent who presented with mixed mood disorder symptoms with psychotic features. Chief complaints were "irritability, regressive behavior, apathy, crying and truancy" which lasted for a year. Premorbid personality was unremarkable with no substance use/exposure or infections. No stressors were present. The patient was not vegetarian. Past medical history and family history was normal. Neurological examination revealed glossitis, ataxia, rigidity in both shoulders, cog-wheel rigidity in the left elbow, bilateral problems of coordination in cerebellar examination, reduced swinging of the arms and masked face. Romberg's sign was present. Laboratory evaluations were normal. Endoscopy and biopsy revealed atrophy of the gastric mucosa with Helicobacter Pylori colonization. Schilling test was suggestive of malabsorbtion. He was diagnosed with Mood disorder with Mixed, Psychotic Features due to Vitamin B12 Deficiency and risperidone 0.5 mg/day and intramuscular vitamin B12 500 mcg/day were started along with referral for treatment of Helicobacter pylori. A visit on the second week revealed no psychotic features. Romberg's sign was negative and cerebellar tests were normal. Extrapyramidal symptoms were reduced while Vitamin B12 levels were elevated. Risperidone was stopped and parenteral Vitamin B12 treatment was continued with monthly injections for 3 months. Follow-up endoscopy and biopsy at the first month demonstrated eradication of H. pylori. He was followed monthly for another 6 months and psychiatric symptoms did not recur at the time of last evaluation. Despite limitations, this case may underline the observation that mood disorders with psychotic features especially with accompanying extrapyramidal symptoms lacking a clear etiology may be rare manifestation of vitamin B12 and/or folate deficiency in children and adolescents and be potentially amenable to treatment.
BMJ Case Rep. 2013 Apr 22;2013. pii: bcr2013008906. doi: 10.1136/bcr-2013-008906.
A rare case of alcoholic pellagra encephalopathy with startle myoclonus and marked response to niacin therapy: time for a new dictum?
Sharma B, Sannegowda RB, Jain R, Dubey P, Prakash S.
Department of Neurology, SMS Medical College Hospital, Jaipur, Rajasthan, India. email@example.com
We report a case of 56-year-old man, chronic alcoholic, presented to us with progressive weakness in all the four limbs with stiffness and gait disturbance since 1-year associated with cognitive impairment. On examination he had mild confusion, spastic quadriparesis with brisk reflexes, extensor plantars and cerebellar features. During the hospital stay myoclonus was noticed in the patient, which was startle in nature. He did not have dermatitis, ascites or any stigmata of liver failure. MRI of brain revealed bilateral subdural effusion, left focal subarachnoid haemorrhage at perisylvian area and diffuse cortical atrophy. He was treated with supportive measures including thiamine with which his condition worsened. His serum niacin was low. With a possibility of alcoholic pellagra encephalopathy (APE) the patient was treated with niacin. His clinical condition improved drastically over next 1 week and startle myoclonus disappeared, favouring the diagnosis of APE though multiple confounding factors were present.
Brain Dev. 2011 Oct;33(9):790-5. doi: 10.1016/j.braindev.2011.06.001. Epub 2011 Jul 20.
Epilepsy in children with methylmalonic acidemia: electroclinical features and prognosis.
Ma X, Zhang Y, Yang Y, Liu X, Yang Z, Bao X, Qin J, Wu X.
Department of Pediatrics, Peking University First Hospital, Beijing, PR China.
To summarize the electroclinical features and prognosis of epilepsy in children with methylmalonic acidemia (MMA).
The medical records of hospitalized MMA patients associated with epilepsy were retrospectively reviewed. The clinical manifestations, laboratory examination results, and treatment modalities were analyzed.
From 63 pediatric inpatients diagnosed as MMA in Peking University First Hospital from June 1996 to December 2009, 27 children (42.9%) associated with epilepsy were enrolled in this study. These 27 patients were also accompanied with other neurological manifestations including mental retardation or regression (n=22), lethargy (n=10), increased muscle tone (n=8), muscle hypotonia (n=8), recurrent vomiting (n=4), tremor (n=2), ataxia (n=2), and abnormal posture (n=1).The onset age of seizure ranged from 8 days to 11 years. The seizure types included partial seizure (n=21), generalized tonic-clonic seizure (n=5), tonic seizure (n=3), myoclonic seizure (n=3), and epileptic spasms (n=2). Five patients had two or three seizure types. Nine patients (33.3%) had a history of status epilepticus. EEG showed slow background activity in 17 patients, focal or multifocal paroxysmal discharges in 16 patients, generalized paroxysmal discharges in four patients, hypsarrythmia in two patients, and suppression-burst pattern in one patient. Cranial MRI scans showed bilateral cerebral atrophy (n=14), increased T2 signal intensities in white matter (n=12), agenesis of corpus callosum (n=2), bilateral increased T2 signal intensities or necrosis in basal ganglia (n=2), and cerebellar atrophy (n=1). Twenty one patients were MMA combined with homocysteinemia. Seventeen patients were confirmed with cobalamin C disease and one with partial mutase deficiency (mut(-)). Vitamin B12-responsive patients had a better outcome compared with vitamin B12-unresponsive patients.
Epilepsy is a common manifestation of patients with MMA. Partial seizure is more common than other seizure types. Urine organic acid analysis should be performed for children with unknown cause of epilepsy combined with other neurological manifestations, so as to promptly identify the etiology and improve the prognosis.
Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
Neuropsychopharmacology. 2007 Oct;32(10):2229-37. Epub 2007 Feb 14.
Cerebellar gray matter volume correlates with duration of cocaine use in cocaine-dependent subjects.
Sim ME, Lyoo IK, Streeter CC, Covell J, Sarid-Segal O, Ciraulo DA, Kim MJ, Kaufman MJ, Yurgelun-Todd DA, Renshaw PF.
Department of Psychiatry, Seoul National University College of Medicine, Seoul 110-744, South Korea.
This study was conducted to explore differences in gray and white matter volume between cocaine-dependent and healthy comparison subjects using optimized voxel-based morphometry (VBM). Brain magnetic resonance imaging (MRI) and neuropsychological function tests were performed for 40 cocaine-dependent subjects (41.4+/-6.9 years, 27 men) and 41 healthy age- and sex-matched comparison subjects (38.7+/-8.8 years, 26 men). Optimally normalized whole brain MR images were segmented, modulated, smoothed, and compared between groups with statistical parametric mapping. The cocaine-dependent group had lower gray matter volumes in bilateral premotor cortex (Brodmann area (BA) 6, 8; 16.6%), right orbitofrontal cortex (BA 10, 15.1%), bilateral temporal cortex (BA 20, 38; 15.9%), left thalamus (12.6%), and bilateral cerebellum (13.4%) as well as lower right cerebellar white matter volume (10.0%) relative to the comparison group at a corrected p<0.05 for multiple comparisons. Duration of cocaine use negatively correlated with right and left cerebellar gray matter volumes (r=-0.37, r=-0.39, respectively). In cocaine-dependent subjects, lower cerebellar hemispheric gray and white matter volumes were correlated with deficits in executive function and decreased motor performance. This study reports that cocaine-dependent subjects have lower gray matter volumes in cerebellar hemispheres as well as in frontal, temporal cortex, and thalamus. These findings are the first to suggest that the cerebellum may be vulnerable to cocaine-associated brain volume changes, and that cerebellar deficits may contribute to neuropsychological deficits and motor dysfunction frequently observed in cocaine-dependent subjects.
Cocaine blocks norepinephrine, serotonin, dopamine, and other neurotransmitters from being reabsorbed.
Tohoku J Exp Med. 2007 Jan;211(1):95-6; author reply 97.
Cerebral folate deficiency and folinic acid treatment in hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) syndrome.
Mercimek-Mahmutoglu S, Stockler-Ipsiroglu S.
Effective treatment with levodopa and carbidopa for hypomyelination with atrophy of the basal ganglia and cerebellum. [Tohoku J Exp Med. 2006]
Tohoku J Exp Med. 2006 Jun;209(2):163-7.
Effective treatment with levodopa and carbidopa for hypomyelination with atrophy of the basal ganglia and cerebellum.
Wakusawa K, Haginoya K, Kitamura T, Togashi N, Ishitobi M, Yokoyama H, Higano S, Onuma A, Nara T, Iinuma K.
Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryomachi, Sendai 980-8574, Japan. firstname.lastname@example.org
Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare leukoencephalopathy presenting in the infantile period and characterized by diffuse cerebral hypomyelination, and atrophy of the basal ganglia and cerebellum. As patients with H-ABC lack remarkable laboratory findings, the diagnosis is based on brain magnetic resonance imaging findings alone. Only eight cases have been reported in the literature, and thus the natural course and treatment of this disease are not fully understood. We report a 35-month-old boy with H-ABC who had hemidystonia, hypomyelination, and cerebellar ataxia. We diagnosed H-ABC after considering a thorough differential diagnosis, excluding other diseases involving hemidystonia, hypomyelination, and cerebellar ataxia. Furthermore, technetium-99m ethyl cysteinate dimmer-single-photon emission computerized tomography (Tc-ECD-SPECT) and positron emission tomography with fluorodeoxyglucose (18)F (FDG-PET) revealed decreased blood flow and glucose metabolism in the bilateral lenticular nucleus, thalamus, and cerebellum. A peroral levodopa preparation containing carbidopa (levodopa-carbidopa) was effective at ameliorating and stopping the progression of the patient's dystonia (final effective doses: levodopa, 200 mg/day and carbidopa, 20 mg/day). This is the first case report of a Japanese patient with H-ABC and treatment for this disease. Levodopa-carbidopa may be an effective treatment for H-ABC.
Rinsho Shinkeigaku. 1990 Nov;30(11):1232-7.
[A case of membranous lipodystrophy (Nasu) with diffuse cerebral white matter involvement and cerebellar atrophy on brain CT and MRI].
[Article in Japanese]
Shibata K, Uchiyama S, Takeuchi M, Kobayashi I, Maruyama S.
Department of Neurology, Tokyo Women's Medical College.
A 37-year-old female was admitted to our hospital because of progressive dementia and gait disturbance. She was healthy until 34 years of age when she had difficulty in walking and memory disturbance with personality changes. At age 36, she developed urinary incontinence and dementia. The neurological examination demonstrated euphoric mental state, emotional incontinence, severe dementia, paraplegia, dysmetria, choreic movements in both arms and urinary incontinence. Diffuse hyperreflexia and bilateral Babinski signs were observed. Routine laboratory examination showed slightly increased erythrocyte sedimentation rate and alkaline phosphatase. Electroencephalogram revealed diffuse irregular slow waves. X-ray film of the ulnar bone revealed osteoporotic and cystic lesions. The biopsy of the left tibial bone showed a specific membranous cystic structure. Computerized tomography (CT) of the brain showed symmetric, diffuse low density areas in the cerebral white matter and severe atrophy of the cerebellum. T2-weighted magnetic resonance imaging (MRI) revealed diffuse high intensity areas in the cerebral white matter. The present case is characterized by diffuse changes in cerebral white matter and cerebellar atrophy, which have been never reported in Nasu-Hakola disease. The diffuse cerebral white matter changes shown by CT and MRI appear to indicate that this patient is the first case of leukodystrophy of sudanophilic type since the original case reported by Nasu et al.
Int J Mol Epidemiol Genet. 2011;2(2):114-21. Epub 2011 Feb 10.
Plasma alkaline phosphatase is elevated in Alzheimer's disease and inversely correlates with cognitive function.
Kellett KA, Williams J, Vardy ER, Smith AD, Hooper NM.
Alkaline phosphatase is present on neuronal membranes and plasma alkaline phosphatase activity increases in brain injury and cerebrovascular disease, suggesting that plasma alkaline phosphatase may partly reflect neuronal loss. As neuronal loss occurs in Alzheimer's disease (AD), we hypothesised that alterations in plasma alkaline phosphatase activity may correlate with cognitive impairment. Plasma alkaline phosphatase activity was measured in the longitudinal Oxford Project to Investigate Memory and Aging (OPTIMA) cohort (121 AD patients, 89 mild cognitive impairment (MCI) patients and 180 control subjects). Plasma alkaline phosphatase activity was significantly higher in the AD patients relative to the controls (p<0.001). In the MCI patients, plasma alkaline phosphatase was at a level in between that seen in control and AD subjects, consistent with the clinical status of this group. Furthermore, plasma alkaline phosphatase activity inversely correlated with cognitive function (assessed by the Cambridge Examination for Mental Disorders (CAMC0G)) in controls (z= -2.21 p=0.027), MCI (z= -2.49, p=0.013) and AD patients (z= -3.61, p=0.0003). These data indicate that plasma alkaline phosphatase activity is increased in AD and inversely correlates with cognitive function regardless of diagnostic status.
Alkaline phosphatase, Alzheimer's, cognitive function, mild cognitive impairment, plasma
J Physiol Biochem. 2011 Dec;67(4):519-30. doi: 10.1007/s13105-011-0097-z. Epub 2011 May 27.
Acetyl-L-carnitine prevents carbon tetrachloride-induced oxidative stress in various tissues of Wistar rats.
Annadurai T, Vigneshwari S, Thirukumaran R, Thomas PA, Geraldine P.
Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli, 620 024, Tamil Nadu, India.
Acetyl-L-carnitine (ALCAR) has been shown to prevent experimental selenite cataractogenesis, a manifestation of oxidative stress, but little is known about its potential in other settings of oxidative stress. The present study was based on the hypothesis that ALCAR prevents carbon tetrachloride (CCl(4))-induced oxidative stress in vital tissues. Male albino Wistar rats were divided into three groups, each of six rats. Group I (control) rats received only vehicle (1 ml/kg b.w.) for 4 days; Group II (CCl(4)-exposed, untreated) rats received CCl(4) (2 ml/kg b.w.) on the second and third days and vehicle on the first and fourth days; Group III (CCl(4)-exposed, ALCAR-treated) rats received ALCAR (200 mg/kg b.w.) for 4 days and CCl(4) on the second and third days. All administrations were made intraperitoneally. After the experimental period, significantly (P < 0.05) elevated mean serum levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase were observed in Group II rats when compared to Group I and Group III rats. The mean levels of vitamin C, vitamin E, and reduced glutathione and the mean activities of superoxide dismutase, catalase, and glutathione peroxidase were significantly (P < 0.05) lower in samples of hemolysate and of liver, kidney, and brain tissues of Group II rats than those in Group I and Group III rats. The mean level of lipid peroxidation was significantly (P < 0.05) higher in Group II rats than that in Group I and Group III rats. Moreover, the CCl(4)-induced upregulation of inducible nitric oxide synthase expression was prevented by ALCAR in the liver and brain tissues. These results suggest that ALCAR is able to prevent the CCl(4)-induced oxidative stress.
Food Chem Toxicol. 2010 Nov;48(11):3246-61. doi: 10.1016/j.fct.2010.08.034. Epub 2010 Sep 4.
Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat.
Yousef MI, Omar SA, El-Guendi MI, Abdelmegid LA.
Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt. email@example.com
The present study was carried out to evaluate the potential protective role of quercetin and curcumin against paracetamol-induced oxidative injury, liver damage and impairment of kidney function, as well as haematotoxicity in rats. Also, N-acetylcysteine was used to evaluate the potency of quercetin and curcumin. Paracetamol caused an elevation in thiobarbituric acid-reactive substances (TBARS) paralleled with significant decline in glutathione peroxidase, glutathione S-transferase, superoxide dismutase and catalase activities (in plasma, brain, lung, heart, liver, kidney and testes) and glutathione content (in lung, liver and kidney). The apparent oxidative injury was associated with evident hepatic necrosis confirmed in histological examination, elevated plasma transmainases, alkaline phosphatase and lactate dehydrogenase. Paracetamol reduced plasma total protein, albumin and globulin, while increased bilirubin, urea and creatinine, and induced haematotoxicity. The presence of quercetin or curcumin with paracetamol successfully mitigated the rise in TBARS and restored the activities of antioxidant enzymes compared to the group treated with both paracetamol and N-acetylcysteine. They also protected liver histology, normalized liver and kidney functions, which was more pronounced with curcumin. Therefore, it can be concluded that concomitant administration of quercetin or curcumin with paracetamol may be useful in reversing the toxicity of the drug compared to N-acetylcysteine.
Copyright © 2010 Elsevier Ltd. All rights reserved.
Toxicol Ind Health. 2011 Nov;27(10):923-33. doi: 10.1177/0748233711399324. Epub 2011 Apr 21.
Protective effect of chrysin on carbon tetrachloride (CCl4)-induced tissue injury in male Wistar rats.
Anand KV, Anandhi R, Pakkiyaraj M, Geraldine P.
Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamil Nadu, India.
Chrysin, a natural flavonoid has been reported to possess potent anti-inflammatory, anti-cancer and antioxidation properties. In the present study, we aimed to evaluate the putative protective effect of chrysin, an isoflavone, on carbon tetrachloride (CCl(4))-induced toxicity in male Wistar rats. Intraperitoneal administration of CCl(4) (2 ml/kg) to rats for 4 days resulted in significantly elevated (p < 0.05) serum levels of glutamic oxaloacetic transaminase (SGOT), glutamic pyruvate transaminase (SGPT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), when compared to normal rats. In addition, the tissues (liver, kidney and brain) and haemolysate samples showed considerable increase in levels (p < 0.05) of malondialdehyde (MDA) and lowered levels (p < 0.05) of reduced glutathione (GSH), vitamin C and E when compared to values in normal rats. Quantitative analysis of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (Gpx) exhibited lower activities of these antioxidant enzymes in the tissues and haemolysate of CCl(4)-administered rats. The protective action of chrysin on CCl(4)-induced rat was demonstrated with SGPT, SGOT, ALP and LDH resuming to near normal levels, while the mean levels of GSH and of vitamin C and E were elevated, the mean activities of CAT, SOD and Gpx were enhanced and the mean level of MDA was lowered in the tissue and haemolysate samples when compared to the CCl(4)-exposed untreated rats. The expression of the iNOS gene appeared to be up-regulated in the liver and kidney samples of CCl(4)-exposed untreated rats, whereas in CCl(4)-exposed chrysin-treated rats, the mRNA transcript levels of iNOS approximated normal levels. These results strongly suggest that chrysin is able to prevent the oxidative damage induced by CCl(4) in the liver, brain, kidney and haemolysate of male Wistar rats.
PMID: 21511893 Passion flower.
World J Biol Psychiatry. 2008;9(3):231-5.
Serum markers of brain-cell damage and C-reactive protein are unaffected by electroconvulsive therapy.
Giltay EJ, Kho KH, Blansjaar BA.
GGZ Delfland, Institute of Mental Health, Delft, The Netherlands. firstname.lastname@example.org
The effects of electroconvulsive therapy (ECT) on serum levels of the acute-phase reactant C-reactive protein (CRP) and intracellular enzymes such as alkaline phosphatase (ALP), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine kinase (CK), have received little attention. If brain cells are damaged, CK-BB, LDH and AST levels are expected to show (minor) elevations. We measured serum levels of prolactin, AST, ALT, LDH, ALP, CK and CRP before and 5 min, 30 min, 4 h, 1 day, 2 days, and 3 days after ECT in 15 consecutive patients (eight women and seven men; mean 53.9 years old, range 3082) who did not receive ECT in the preceding 2 weeks. Prolactin levels increased (P = 0.001), but none of the other mean concentrations significantly increased over time. All concentrations remained within the normal range in every patient, except for five samples with elevated CK levels (range 333-675 IU/l). CK-MB and CK-BB fractions, however, remained low, indicating that skeletal muscle was the source of the CK elevation. Serum levels of markers of brain cell leakage and inflammation remained low following one ECT session, suggesting that ECT does not cause direct brain cell leakage, nor an inflammatory response.
Nat Genet. 1995 Sep;11(1):45-51.
Mice lacking tissue non-specific alkaline phosphatase die from seizures due to defective metabolism of vitamin B-6.
Waymire KG, Mahuren JD, Jaje JM, Guilarte TR, Coburn SP, MacGregor GR.
Department of Genetics and Molecular Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
In humans, deficiency of the tissue non-specific alkaline phosphatase (TNAP) gene is associated with defective skeletal mineralization. In contrast, mice lacking TNAP generated by homologous recombination using embryonic stem (ES) cells have normal skeletal development. However, at approximately two weeks after birth, homozygous mutant mice develop seizures which are subsequently fatal. Defective metabolism of pyridoxal 5'-phosphate (PLP), characterized by elevated serum PLP levels, results in reduced levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain. The mutant seizure phenotype can be rescued by the administration of pyridoxal and a semi-solid diet. Rescued animals subsequently develop defective dentition. This study reveals essential physiological functions of TNAP in the mouse.
PMID: 7550313 [