Cortical cerebral metabolism correlates with MRI lesion load and cognitive dysfunction in MS

Objective: To study the association between the cortical cerebral metabolic rate of glucose (CMRglc), MRI T2-weighted total lesion area (TLA), cognitive dysfunction, and neurologic disability in MS. Background: MRI lesion load is widely used in the clinical evaluation of the MS patient but little is known about the associated changes in cortical activation. Methods: Twenty-three patients with clinically definite MS underwent measurements of CMRglc, TLA, motor evoked potentials (MEPs), and cognitive and neurologic disability. CMRglc was calculated using PET and 18-F-deoxyglucose and compared with nine normal control subjects. Results: Reductions in CMRglc (p < 0.01) were found in the cortical global and regional lobar measurements. Furthermore, regional CMRglc (rCMRglc) was reduced in the dorsolateral prefrontal cortex, orbitofrontal cortex, caudate, putamen, thalamus, and hippocampus. Global cortical CMRglc correlated with TLA (Spearman rank correlation coefficient [SRCC] = −0.66, p = 0.001), and rCMRglc correlated with regional lesion load in all cerebral lobes (p ≤ 0.05). Global cortical CMRglc and cognitive disability also correlated (SRCC = 0.58, p = 0.015), and stepwise regression analysis showed a significant association between rCMRglc of the right thalamus and cognitive performance as well as TLA. There was no correlation between CMRglc and neurologic disability (Expanded Disability Status Scale) or MEP. Conclusion: Global and regional cortical CMRglc is reduced significantly in MS patients compared with normal control subjects. Furthermore, the CMRglc reductions correlate with TLA as well as with cognitive dysfunction, which indicates that MRI white matter lesion burden has a deteriorating effect on cortical cerebral neural function.

[1]  J. Kastrup,et al.  Intravenous lidocaine infusion — a new treatment of chronic painful diabetic neuropathy? , 1987, Pain.

[2]  L Bozzao,et al.  SPECT, MRI and cognitive functions in multiple sclerosis. , 1991, Journal of neurology, neurosurgery, and psychiatry.

[3]  J. Kastrup,et al.  The effect of intravenous lidocaine on nociceptive processing in diabetic neuropathy , 1990, Pain.

[4]  A. Gade,et al.  Visuel closure—Street completion test , 1988 .

[5]  E. Kalso,et al.  Systemic local‐anaesthetic‐type drugs in chronic pain: A systematic review , 1998, European journal of pain.

[6]  M. L. Sotgiu,et al.  Selective inhibition by systemic lidocaine of noxious evoked activity in rat dorsal horn neurons. , 1991, Neuroreport.

[7]  S L Shafer,et al.  Prolonged Alleviation of Tactile Allodynia by Intravenous Lidocaine in Neuropathic Rats , 1995, Anesthesiology.

[8]  L. Arendt-Nielsen,et al.  NMDA receptor blockade in chronic neuropathic pain: a comparison of ketamine and magnesium chloride , 1996, Pain.

[9]  R. Burney,et al.  Intravenous Lidocaine in the Management of Various Chronic Pain States: A Review of 211 Cases , 1985, Regional Anesthesia & Pain Medicine.

[10]  T. Greitz,et al.  A computerized brain atlas: construction, anatomical content, and some applications. , 1991, Journal of computer assisted tomography.

[11]  C V Jensen,et al.  A longitudinal study of cerebral glucose metabolism, MRI, and disability in patients with MS , 1999, Neurology.

[12]  P. Eide,et al.  Central dysesthesia pain after traumatic spinal cord injury is dependent on N-methyl-D-aspartate receptor activation. , 1995, Neurosurgery.

[13]  A. Gade,et al.  On the relation between demographic variables and neuropsychological test performance , 1993 .

[14]  J. Kurtzke.  Rating neurologic impairment in multiple sclerosis , 1983, Neurology.

[15]  P. A. Beatty,et al.  Anterograde and retrograde amnesia in patients with chronic progressive multiple sclerosis. , 1988, Archives of neurology.

[16]  M. Blinkenberg,et al.  Standardization of facilitation of compound muscle action potentials evoked by magnetic stimulation of the cortex. Results in healthy volunteers and in patients with multiple sclerosis. , 1991, Electroencephalography and clinical neurophysiology.

[17]  A. Thompson,et al.  Spinal cord MRI using multi‐array coils and fast spin echo , 1993, Neurology.

[18]  V. Haughton,et al.  Correlation of magnetic resonance imaging with neuropsychological testing in multiple sclerosis , 1989, Neurology.

[19]  F. Barkhof,et al.  Guidelines for the use of magnetic resonance techniques in monitoring the treatment of multiple sclerosis , 1996, Annals of neurology.

[20]  D. Tanelian,et al.  Neuropathic pain can be relieved by drugs that are use-dependent sodium channel blockers: lidocaine, carbamazepine, and mexiletine. , 1991, Anesthesiology.

[21]  M Filippi,et al.  Correlation between brain MRI lesion volume and disability in patients with multiple sclerosis , 1996, Acta neurologica Scandinavica.

[22]  M. Rowbotham,et al.  Response to intravenous lidocaine infusion differs based on clinical diagnosis and site of nervous system injury , 1993, Neurology.

[23]  H. Buerkle,et al.  Lidocaine concentrations in plasma and cerebrospinal fluid after systemic bolus administration in humans. , 1998 .

[24]  W. Ammann,et al.  Reduced glucose metabolism in the frontal cortex and basal ganglia of multiple sclerosis patients with fatigue , 1997, Neurology.

[25]  G J Barker,et al.  Serial proton magnetic resonance spectroscopy in acute multiple sclerosis lesions. , 1994, Brain : a journal of neurology.

[26]  Michael F. Ferrante.  Pain and Central Nervous System Disease. The Central Pain Syndromes , 1992 .

[27]  P M Grasby,et al.  Brain systems for encoding and retrieval of auditory-verbal memory. An in vivo study in humans. , 1995, Brain : a journal of neurology.

[28]  Kim Hansen,et al.  COGNITIVE DYSFUNCTION IN A POPULATION-BASED SAMPLE OF MULTIPLE SCLEROSIS PATIENTS , 1998 .

[29]  R. Knobler,et al.  Neuropsychological and structural brain lesions in multiple sclerosis , 1992, Neurology.

[30]  R. Sandyk,et al.  Mexiletine for thalamic pain syndrome. , 1990, The International journal of neuroscience.

[31]  R. Kupers,et al.  Systemic lidocaine induces expansion of the receptive field of spinal dorsal horn neurons in rats , 1998, Experimental Brain Research.

[32]  C. Woolf,et al.  Lignocaine selectively reduces C fibre-evoked neuronal activity in rat spinal cord in vitro by decreasing N-methyl-d-aspartate and neurokinin receptor-mediated post-synaptic depolarizations; implications for the development of novel centrally acting analgesics , 1996, Pain.

[33]  S. Kondo,et al.  Clinical significance of reduced cerebral metabolism in multiple sclerosis: A combined PET and MRI study , 1998, Annals of nuclear medicine.

[34]  U. Lindblom,et al.  Systemic mexiletine relieves chronic allodynialike symptoms in rats with ischemic spinal cord injury. , 1992, Anesthesia and analgesia.

[35]  C. V. Jensen,et al.  Cerebral metabolism in a case of multiple sclerosis with acute mental disorder , 1996, Acta neurologica Scandinavica.

[36]  J D Brodie,et al.  Intersubject variability of brain glucose metabolic measurements in young normal males. , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[37]  Richard S. J. Frackowiak,et al.  Brain regions associated with acquisition and retrieval of verbal episodic memory , 1994, Nature.

[38]  A. Pertovaara,et al.  Lidocaine in the rostroventromedial medulla and the periaqueductal gray attenuates allodynia in neuropathic rats , 1996, Neuroscience Letters.

[39]  L. C. Russell,et al.  Pain response to perineuromal injection of normal saline, epinephrine, and lidocaine in humans , 1992, Pain.

[40]  S. Tuel,et al.  Effect of mexiletine on spinal cord injury dysesthetic pain. , 1996, American journal of physical medicine & rehabilitation.

[41]  C. Woolf,et al.  The systemic administration of local anaesthetics produces a selective depression of C-afferent fibre evoked activity in the spinal cord , 1985, Pain.

[42]  J. Ridley.  Studies of Interference in Serial Verbal Reactions , 2001 .

[43]  M. Reivich,et al.  THE [14C]DEOXYGLUCOSE METHOD FOR THE MEASUREMENT OF LOCAL CEREBRAL GLUCOSE UTILIZATION: THEORY, PROCEDURE, AND NORMAL VALUES IN THE CONSCIOUS AND ANESTHETIZED ALBINO RAT 1 , 1977, Journal of neurochemistry.

[44]  M. Swerdlow,et al.  Anticonvulsant drugs used in the treatment of lancinating pain. A comparison , 1981, Anaesthesia.

[45]  L. Jacobsson,et al.  Regional Cerebral Blood Flow in Multiple Sclerosis Measured by Single Photon Emission Tomography with Technetium-99m Hexamethyl-propyleneamine Oxime , 1993 .

[46]  J Marshall,et al.  Studies on regional cerebral oxygen utilisation and cognitive function in multiple sclerosis. , 1984, Journal of neurology, neurosurgery, and psychiatry.

[47]  T. Yaksh,et al.  Systemic Lidocaine Blocks Nerve Injury‐induced Hyperalgesia and Nociceptor‐driven Spinal Sensitization in the Rat , 1994, Anesthesiology.

[48]  H. Buerkle,et al.  Lidocaine Concentrations in Plasma and Cerebrospinal Fluid After Systemic Bolus Administration in Humans , 1998, Anesthesia and analgesia.

[49]  J. Mazziotta,et al.  Rapid Automated Algorithm for Aligning and Reslicing PET Images , 1992, Journal of computer assisted tomography.

[50]  Karl J. Friston,et al.  A graded task approach to the functional mapping of brain areas implicated in auditory-verbal memory. , 1994, Brain : a journal of neurology.

[51]  D. Crockett.  A comparison of empirically derived groups of aphasic patients on the Neurosensory Center Comprehensive Examination for Aphasia. , 1977, Journal of clinical psychology.

[52]  Salahadin Abdi,et al.  The Anti-Allodynic Effects of Amitriptyline, Gabapentin, and Lidocaine in a Rat Model of Neuropathic Pain , 1998, Anesthesia and analgesia.

[53]  R K Simpson,et al.  Systemic Lidocaine Therapy for Poststroke Pain , 1993, Southern medical journal.

[54]  R. Heaton,et al.  Correlation of neuropsychological and MRI findings in chronic/progressive multiple sclerosis , 1988, Neurology.

[55]  G. R. Arthur,et al.  The Analgesic Response to Intravenous Lidocaine in the Treatment of Neuropathic Pain , 1996, Anesthesia and analgesia.

[56]  D. Wechsler.  Wechsler Adult Intelligence Scale , 2021, Encyclopedia of Evolutionary Psychological Science.

[57]  H. Fruhstorfer,et al.  Method for quantitative estimation of thermal thresholds in patients. , 1976, Journal of neurology, neurosurgery, and psychiatry.

[58]  L. C. Russell,et al.  Pain responses to perineuromal injection of normal saline, gallamine, and lidocaine in humans , 1989, Pain.

[59]  M. L. Sotgiu,et al.  Lidocaine test in neuralgia , 1992, Pain.

[60]  F. Barkhof,et al.  Accumulation of hypointense lesions ("black holes") on T1 spin-echo MRI correlates with disease progression in multiple sclerosis , 1996, Neurology.

[61]  I Litvan,et al.  Multiple memory deficits in patients with multiple sclerosis. Exploring the working memory system. , 1988, Archives of neurology.

[62]  E. Hoffman,et al.  Noninvasive determination of local cerebral metabolic rate of glucose in man. , 1980, The American journal of physiology.

[63]  M. L. Sotgiu,et al.  Central effects of systemic lidocaine mediated by glycine spinal receptors: an iontophoretic study in the rat spinal cord , 1993, Brain Research.

[64]  M. Rowbotham,et al.  Both intravenous lidocaine and morphine reduce the pain of postherpetic neuralgia , 1991, Neurology.

[65]  B. Brownell,et al.  The distribution of plaques in the cerebrum in multiple sclerosis , 1962, Journal of neurology, neurosurgery, and psychiatry.

[66]  D. Paty,et al.  Interferon beta‐1b is effective in relapsing‐remitting multiple sclerosis , 1993, Neurology.

[67]  G. Barker,et al.  Correlation of magnetization transfer ration with clinical disability in multiple sclerosis , 1994, Annals of neurology.

[68]  P. Matthews,et al.  Chemical pathology of acute demyelinating lesions and its correlation with disability , 1995, Annals of neurology.

[69]  C. D. Arnett,et al.  Glucose Metabolic Rate Kinetic Model Parameter Determination in Humans: The Lumped Constants and Rate Constants for [18F]Fluorodeoxyglucose and [11C]Deoxyglucose , 1985, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[70]  R. Simpson,et al.  Systemic lidocaine therapy for poststroke pain. , 1993 .

[71]  J. Usubiaga,et al.  Relationship between the passage of local anaesthetics across the blood-brain barrier and their effects on the central nervous system. , 1967, British journal of anaesthesia.

[72]  Patrick D. Wall,et al.  Systemic lidocaine silences ectopic neuroma and DRG discharge without blocking nerve conduction , 1992, Pain.

[73]  J. Brande.  A personal view on the early history of the insulin-like growth factors. , 1999 .

[74]  G. Gonzales.  Central pain , 1994, Neurology.

[75]  G. Leijon,et al.  Central post-stroke pain — a controlled trial of amitriptyline and carbamazepine , 1989, Pain.

[76]  HERMAN BUSCHKE,et al.  Evaluating storage, retention, and retrieval in disordered memory and learning , 1974, Neurology.

[77]  M. L. Sotgiu,et al.  Effect of systemic lidocaine on dorsal horn neuron hyperactivity following chronic peripheral nerve injury in rats. , 1992, Somatosensory & motor research.

[78]  Edward E. Smith,et al.  Spatial working memory in humans as revealed by PET , 1993, Nature.

[79]  M. L. Sotgiu,et al.  Diverse modulation by systemic lidocaine of iontophoretic NMDA and quisqualic acid induced excitations on rat dorsal horn neurons , 1993, Neuroscience Letters.

[80]  Karl J. Friston,et al.  Activation of the human hippocampal formation during auditory-verbal long-term memory function , 1993, Neuroscience Letters.

[81]  A J Thompson,et al.  Progressive cerebral atrophy in multiple sclerosis. A serial MRI study. , 1996, Brain : a journal of neurology.

[82]  E. Rota Kops,et al.  Performance characteristics of an eight-ring whole body PET scanner. , 1990, Journal of computer assisted tomography.

[83]  M. Rowbotham,et al.  Response to intravenous lidocaine infusion predicts subsequent response to oral mexiletine: a prospective study. , 1996, Journal of pain and symptom management.

[84]  G. E. Alexander,et al.  Parallel organization of functionally segregated circuits linking basal ganglia and cortex. , 1986, Annual review of neuroscience.

[85]  M. L. Sotgiu,et al.  Different time-courses of i.v. lidocaine effect on ganglionic and spinal units in neuropathic rats. , 1994, Neuroreport.

[86]  T. Shallice.  Specific impairments of planning. , 1982, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[87]  Marianne Regard,et al.  Children's Production on Verbal and Non-Verbal Fluency Tasks , 1982, Perceptual and motor skills.

[88]  E. Kaplan,et al.  The Boston naming test , 2001 .

[89]  D. Drachman,et al.  Thalamic dementia and motor neuron disease , 1989, Neurology.

[90]  H. Nelson.  A Modified Card Sorting Test Sensitive to Frontal Lobe Defects , 1976, Cortex.

[91]  D. Silberberg,et al.  New diagnostic criteria for multiple sclerosis: Guidelines for research protocols , 1983, Annals of neurology.

[92]  O B Paulson,et al.  Calculation of the FDG Lumped Constant by Simultaneous Measurements of Global Glucose and FDG Metabolism in Humans , 1998, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[93]  M. Backonja,et al.  Response of central pain syndromes to intravenous lidocaine. , 1992, Journal of pain and symptom management.

[94]  F. Fazio,et al.  Functional Basis of Memory Impairment in Multiple Sclerosis: A [18F]FDG PET Study , 1996, NeuroImage.

[95]  H. Yonas,et al.  Thalamic and subcortical gliosis with dementia. , 1987, Archives of neurology.