Differential Diagnosis 1 – Weeks 3 & 4

Differential Diagnosis 1 – Weeks 3 & 4

Seizures Although approximately 6% of adults will experience at least one afebrile seizure in their lifetime, only 0.5% will have recurring seizures (epilepsy) (So and Hauser ref). This must be considered prior to initiating medical management decisions. So NK. Recurrence, remission, and relapse of seizures. Cleve Clin J Med 1993;60:439-443. Hauser WAS, Rich SS, Annegers JF, Anderson VE. Seizure recurrence after a 1st unprovoked seizure: an extended follow-up. Neurology 1990;40:1163-1167. Twenty-four percent of epileptic patients are elderly with 38% of new cases occurring in the elderly (with stroke accounting for one-third of cases). (Stephen ref) Stephen LJ. Epilepsy in elderly people. Lancet 2000;355:4-8.

Seizures or Convulsions • Was there a hypoxic event? • Distinguish syncope from epileptic event • Occur only with fever? • Use or sudden withdrawal from prescribed or ilicit drug? • Family and personal history of attacks? • Search for localizing signs and individual triggers

Age-Relationship to Seizures Infancy- childhood: developmental, infection, trauma, cerebrovascular disease (CVD) Adult – brain tumor, trauma, developmental disorder, infection, CVD Late adulthood-elderly: CVD, brain tumor, degenerative disease, trauma

Theories • Neurogenesis – based on animal models it appears that seizures can trigger increased mitotic activity in the dentate gyrus (specific to temporal lobe epilepsy) increasing differentiation and creation of new dentate granule cells • Mousy-fiber sprouting – found with temporal lobe epilepsy. These extend to pyramidal neurons as part of the hippocampal output pathway.

Cortical malformations – may be involved with partial or generalized epilepsy. • Theory is based on a disruption of development in the cerebral cortex classified as disorders of neuronal proliferation, neuronal migration, or disruption or re-organization of the cortex. • These may be involved more with refractory epilepsy and specifically in cases once believed to be cryptogenic. • Neurons within dysplastic areas may lack potassium channels or GABA-mediated inhibitory mechanisms.

Glial cell – glial cells, although primarily supportive, also serve functions of buffering that help maintain uptake of potassium and glutamate (among other metabolic balances). The result may be increased levels of extracellular potassium decreasing the threshold for neuronal firing (hyeprexcitability). • Chang BS, Lowenstein DH. Epilepsy. N Engl J Med 2003;349:1257-1266.

Table C30-1. Loci of origin of simple focal seizures • Motor - Movement of any part of the motor homunculus, sometimes with aphasia • Somatosensory - Contralateral numbness or tingling of face, fingers, or toes • Primary visual cortex - Flashes of light or patches of darkness in contralateral visual field • Visual association cortex -Twinkling light images in contralateral visual field • Basal occipitotemporal junction - Formed visual images of people or places, sometimes accompanied by sounds • Superior temporal gyrus (unusual) - Tinnitus, sometimes garbled word sounds

The Normal Thalamocortical Circuit and EEG Patterns during Wakefulness, Non-Rapid-Eye-Movement (Non-REM) Sleep, and Absence Seizures Chang B and Lowenstein D. N Engl J Med 2003;349:1257-1266

Medical Treatment & Possible Side-Effects Valproic acid (Depacon) – tremor and weight gain Phenytoin (Dilantin)– in young patients gingival hyperplasia and hirsutism Carbamazapine (Carbatrol, Tegretol, Tegretol-XR) and oxcarbazepine (Trileptal) - hyponatremia in patients who drink large amounts of fluids or on diuretics

Other Tx Options Various surgical options – usually for those with a well-defined structural lesion Vagal nerve simulation Deep brain stimulation Ketogenic diet

Surgical Options For refractive epilepsy there are several options dependent on the type, age, location and type of lesion. Following is a list of current surgical options with related types that may be treated (Nguyen ref): Resective surgery – the epiloptogenic area must be delineated using several approaches to a convergent localization that allows accuracy in resection. Temporal lobe epilepsy is one example of epilepsy that may be responsive to resection. Multiple Subpial transactions – based on the knowledge that functional cortical organization is primarly vertical. Intracortical fibers that are generally responsible for seizures are horizontally oriented. Small parallel cortical slices are made perpendicular to the long axis of the gyrus in an effort to spare function. This procedure is used alone or in combination with resective surgery for seizures arising in or around motor, sensory, or language cortical areas. Gamma-Knife surgery – This is a stereotactic delivery of radiation to a very specific point in the brain which has been identified using MRI. There is a delay effect in results that may occur as much as one to three years post-procedure. Currently, three types of epilepsy are being evaluated for success using this treatment including hypothalamic hamartomas, vascular malformations, and mesial temporal lobe sclerosis. In selected cases, success rates for cessation of seizures is around 75%.

Options for Epilepsy • Vagal nerve stimulation – this is an adjunctive therapy with an effect of desynchronizing the EEG the left vagal nerve stimulation through a subcutaneous lead. The device may decrease frequency of seizures by about 25% but is not used as a cure-all. • Deep brain stimulation – stimulation of areas including the anterior thalamus, the cetromedian thalamic nucleus, the caudate nucleus, the posterior hypothalamus, and hippocampus have been experimented with. Multicenter studies are now underway to determine effectiveness. Nguyen DK, Spencer SS. Recent advances in the treatment of epilepsy. Arch Neurol 2003;60:929-935.

Types of Memory • Declarative (explicit) – facts, events • Nondeclarative (implicit) – skills and habits, priming, simple classic conditioning, nonassociate learning • Amnesia is an example of simple declarative loss; two types: antegrade and retrograde • Attention/Registration - < 1 sec. • Working – seconds to minutes • Consolidation – minutes to years

Memory Creation For long-term memory the postsynaptic cell needs to stimulate the manufacture of synapse-strengthening proteins (CREB proteins) that might then add more receptors or change the post-synaptic response in some way Information that is declarative (people, places, events) must pass through the hippocampus before being recorded in the cerebral cortex.

Primary Causes and Differences in Adults • Multi-Infarct Dementia - Sudden onset with associated neurological deficits that are often motor or sensory • Depression – memory loss is often profound; referred to as “pseudo-dementia” look for other indicators of depression • Age-Related Memory Loss – slow in onset, related only to learning new events (can’t teach an old dog new tricks) • Medication or Metabolic Related – relatively sudden onset timed with administration of medication or onset of other symptoms/signs; tested with laboratory

Alzheimer Disease • characterized by significant loss of memory and cognitive functions • subiculum and entorhinal cortex are among first sites where degenerative changes occur (hippocampus proper is also involved) relay of information through hippocampal formation is markedly affected • this damage is at least partially responsible for memory deficits seen in Alzheimer disease • Alzheimer’s is a progressive, neurological disease characterized by neurofibrillary tangles and plaques made of tau protein.

Medical Management cholinesterase inhibitors (tacrine [Cognex] donepaxil [Aricept]) yet this tx does not alter the course of the disease memantine, is an uncompetitive NMDA-receptor antagonist (anti-glutamatergic) Aspirin may be preventive Estrogen, Ginko-biloba, and memory games have been shown to have no effect The only apparent effective therapy is aerobic exercise

References for Aerobic Exercise and the Brain: Preliminary Evidence Aerobic exercise training increases brain volume in aging humans. Colcombe SJ, Erickson KI, Scalf PE, Kim JS, Prakash R, McAuley E, Elavsky S, Marquez DX, Hu L, Kramer AF. J Gerontol A BiolSci Med Sci. 2006 Nov;61(11):1166-70. Fitness effects on the cognitive function of older adults: a meta-analytic study. Colcombe S, Kramer AF. Psychol Sci. 2003 Mar;14(2):125-30.

Korsakoff Syndrome • condition caused by prolonged thiamine deficiency, typically seen in chronic alcoholics • causes a characteristic pattern of brain degeneration  typically mammillary bodies, dorsomedial nucleus of thalamus, and columns of fornix are involved  there is also loss of neurons in hippocampal formation • patients have short-term and long-term memory defects for events occurring since onset of disease  patients are prone to confabulations (string together fragments of memory from different events to form a “memory” of an event that never occurred) • in some patients it is accompanied by gaze palsies and ataxia secondary to cerebellar damage  Wernicke-Korsakoff syndrome

Weakness • Differentiate with questioning to determine a sense of fatigue or true muscular weakness • Neuro causes usually involve the distal extremities: determine if: • UMNL • LMNL • Muscular causes usually involve proximal muscle groups • Further differentiation may be needed with EMG/NCV

Neurologic Weakness • Neurologic weakness is painless weakness • Differentiate lower motor problems into either plexus, nerve root, or peripheral nerve problems • Plexus - diffuse symptoms/signs • Nerve root - dermatome, myotome, and sometimes deep tendon reflex effects • Peripheral nerve - specific group of muscles, patch of skin, possible DTR • Referred - no objective neurologic findings

The 3 M’s Misunderstandings Misconceptions Myths

1 The mostcommon cause of cervical radiculopathyis disc herniation

Approximately 80% of radicular presentations are due to foraminal encroachment. Only about 20% are due to a disc herniation

Why not disc herniation as a cause in the cervical spine? Protection from the PLL (posterior longitudinal ligament) The location of the nerve roots/spinal nerve in the IVF The loss of a nucleus pulposis by age 45

Compression Posterior IVF Compression Fibrous tissue in IVF Buckling of ligamentum flavum Osteophytes from superior and inferior articular processes

2 Patients trace a dermatome when they have nerve root involvement

Pain Patterns and Descriptions in Patients with Radicular Pain: Does the Pain Necessarily Follow a Specific Dermatome?Murphy DR, Hurwitz E, Gerrard JK, Clary RChiropractic & Osteopathy 2009; 17:9

Except for C4 . . . . Pain was non-dermatomal in 69.7% cases of cervicalradiculopathy

Except for S1 . . . . Pain was non-dermatomal in 64.1% of cases of lumbarradiculopathy

Why? • A spinal segment does not equal all the nerves that goes to that spinal nerve • For example, sensory nerve fibers in the C5 spinal segment may not contribute to the C5 spinal nerve • Nerve fibers transmitting different sensory modalities to the same skin area may derive from different spinal nerves or different spinal segments • Overlap of innervaton from two spinal nerves may result in no loss of sensation when one is compressed or damaged

3 Patients claim weakness when they have nerve root involvement

In subjects with electrodiagnostic evidence of radicuopathy . . . . . 64%-75% will have weakness on examination Only 15%-34% will complainof weakness

In subjects with electrodiagnostic evidence of radicuopathy . . . . . Lauder TM. Physical Examination Signs, Clinical Symptoms, and Their Relationship to Electrodiagnostic Findings and the Presence of Radiculopathy. Phys Med Rehabil Clin N Am. 2002:451-467 31% will have no weakness on examination 33%-45% will have no sensory abnormalities

Pronation Strength for C6-C7 Although forearm flexion/wrist extension are used for C6 and elbow extension for C7, pronation is an option For C6 – 72% had pronation weakness (wrist extension weak in 36%) For C7 – 23% had pronation weakness with elbow extension weakness; pronation was only weakness in 10% Rainville J, Noto DJ, Jouve C, Jenis L. Assessment of forearm pronation strength in C6 and C7 radiculopathies. Spine. Jan 1 2007;32(1):72-75.

4 The area of numbnessextends throughout the area of pain radiation

5 There is only one muscle that is found weak with each nerve root

L5-S1 Disc Rupture (S1 Nerve Root)

Differential Diagnosis 1 – Weeks 3 & 4