Identification, diagnosis, and treatment of neuropathologies, neurotoxicities, tumors, and brain and spinal cord injuries using microelectrodes with microvoltammetry

A method of monitoring a controlled-substance treatment in a mammal having a neurological disorder comprising:

• generating a temporally and/or spatially resolved Broderick probe microvoltammogram of said mammal:
• determining from said microvoltammogram the presence and concentration of a marker selected from the group consisting of serotonin, dopamine, ascorbic acid, norepinephrine, γ-aminobutyric acid, glutamate, neurotensin, somatostatin, dynorphin, homovanillic acid, uric acid, tryptophan, tyrosine, nitrous oxide, and nitric oxide;
• and
• comparing said marker concentration to a threshold value of said respective marker,
• wherein said threshold value is derived from a Broderick probe microvoltammogram of a mammal that does not have said neurological disorder, wherein the concentration of said marker differs from said threshold value wherein the controlled substance treatment is a treatment selected from the group consisting of opiates, stimulants, and depressants, wherein the opiate is selected from the group consisting of alfentanil, aiphaprodine, anileridine, apomorphine, bezitramide, carfentanil, cocaine, codeine, 4-cyano-2-dimethylamino-4,4-diphenyl butane, 4-cyano-1-methyl-4-phenylpiperidine pethidine-intermediate-B, dextropropoxyphene, dextrorphan, dihydrocodeine, dihydroetorphine, diphenoxylate, 1-diphenylpropane-carboxylic acid pethidine (meperidine), ecgonine, ethyl-4-phenylpiperidine-4-carboxylate pethidine-intermediate-C, ethylmorphine, etorphine hydrochloride, fentanyl, hydrocodone, hydromorphone, isomethadone, levo-alphacetylmethadol, levomethorphan, levorphanol, metazocine, methadone, methadone-intermediate, 2-methyl-3-morpholino- 1,1-methyl-4-phenylpiperidine-4-carboxylic acid, metopon, morphine, moramide-intermediate, nalbuphine, nalmefene, naloxone, naltrexone, opium, oxycodone, oxymorphone, pethidine-intermediate-A, phenanthrene alkaloidsphenazocine, piminodine, racemethorphan, racemorphan, remifentanil, sufentanil, thebaine, and the baine-derived butorphanol.

A method for distinguishing a gray matter tissue from a white matter tissue comprising:

• generating a temporally and/or spatially resolved Broderick probe microvoltammogram of the tissue;
• determining from said microvoltammogram the presence and concentration of a marker selected from the group consisting of serotonin, dopamine, ascorbic acid, norepinephrine, γ-aminobutyric acid, glutamate, neurotensin, somatostatin, dynorphin, homovanillic acid, uric acid, tryptophan, tyrosine, nitrous oxide, and nitric oxide;
• and
• comparing said marker to a threshold value of said respective marker,
• wherein said threshold value is derived from a Broderick probe microvoltammograms of a gray matter tissue selected from the group consisting of neocortical gray, pyramidal layers, and granular cells of the dentate gyrus and
• a white matter tissue selected from the group consisting of temporal stem, alveus, subiculum, and band of baillarger and wherein said step of comparing said marker concentrations distinguishes whether said tissue is gray matter or white matter.

A method of treating temporal lobe epilepsy comprising:

• generating a temporally and/or spatially resolved Broderick probe microvoltammogram of a temporal lobe tissue of a subject in need of such treatment;
• comparing said microvoltammogram to at least one
• reference Broderick probe microvoltammogram;
• determining the type and extent of temporal lobe resection necessary to achieve a substantially seizure free outcome;
• and
• resecting the subject's temporal lobe accordingly;
• wherein said reference microvoltammogram is a Broderick probe microvoltammogram of the corresponding non-epileptogenic temporal lobe tissue of said subject if the subject is human or a non-human mammal having mesial temporal lobe epilepsy or neocortical temporal lobe epilepsy.

A method for determining the grade of a tumor (degree of malignancy) comprising:

• generating a temporally and/or spatially resolved Broderick probe microvoltammogram of a test tissue;
• determining from said microvoltammogram the presence and concentration of at least two markers selected from the group consisting of serotonin, dopamine, ascorbic acid, norepinephrine, γ-aminobutyric acid, glutamate, neurotensin, somatostatin, dynorphin, homovanillic acid, uric acid, tryptophan, tyrosine, nitrous oxide, and nitric oxide;
• and
• comparing said test tissue marker concentrations to threshold values of the markers wherein, said threshold values are derived from Broderick probe microvoltammogram(s) of reference tissue selected from the group consisting of non-cancerous tissue and cancerous tissue.

A method for continuous or intermittent therapeutic monitoring of pharmacologic and nonpharmacologic therapies for brain disorders comprising:

• contacting a brain tissue having a brain disorder selected from the group consisting of disorders of the basal ganglia, epilepsy, multiple sclerosis, bipolar disorder, subarachnoid hemorrhage, hydrocephalus, cerebral infarction, autoimmune disorders and infections of the central nervous system with a Broderick probe;
• administering a pharmacologic and nonpharmacologic therapy;
• applying a potential to said Broderick probe;
• and
• generating a temporally and/or spatially resolved Broderick probe microvoltammogram.

A method for detecting a site of nerve damage or blockage in a mammal comprising:

• contacting a central pattern generator neural network with a Broderick probe;
• applying a potential to said Broderick probe;
• generating a temporally and/or spatially resolved Broderick probe microvoltammogram of said central pattern generator neural network;
• simultaneously monitoring movement behavior of said mammal;
• and
• comparing said microvoltammogram and movement behavior to a reference microvoltammogram and concurrent movement behavior of a mammal that does not have nerve damage or blockage, wherein said step of comparing distinguishes synchrony and/or asynchrony between neurotransmitter in the central pattern generator and movement and indicates nerve damage or blockage, wherein said neurotransmitter is selected from the group consisting of serotonin, dopamine, ascorbic acid, norepinephrine, γ-aminobutyric acid, glutamate, neurotensin, somatostatin, dynorphin, homovanillic acid, uric acid, tryptophan, tyrosine, nitrous oxide, and nitric oxide.

A method for diagnosing brain or spinal cord injury in a mammal comprising:

• contacting a central pattern generator neural network with a Broderick probe;
• applying a potential to said Broderick probe;
• generating a temporally and/or spatially resolved Broderick probe microvoltammogram of said central pattern generator neural network;
• simultaneously monitoring movement behavior of said mammal;
• and
• comparing said microvoltammogram and movement behavior to a reference microvoltammogram and concurrent movement behavior of a mammal that does not have brain or spinal cord injury;
• wherein said comparing step distinguishes synchrony and/or asynchrony between neurotransmitter in the central pattern generator and movement and indicates brain or spinal cord injury, wherein said neurotransmitter is selected from the group consisting of serotonin, dopamine, ascorbic acid, norepinephrine, γ-aminobutyric acid, glutamate, neurotensin, somatostatin, dynorphin, homovanillic acid, uric acid, tryptophan, tyrosine, nitrous oxide, and nitric oxide.