Altered Sensorium SGD (Advanced Trans)

SGD 2: Altered Sensorium

OS 212 Neurology Neuro Consultants

Exam 1

November 10, 2008, | Thursday Page 1 of 5

Ikey and Lee

Outline

I. The Case II. The Questions Hi Block A. Considering the rush job we put together in an attempt to get this trans out in a timely manner, not to mention the fact that this case is different from last year’s, we hope you’ll pardon whatever errors and omissions are exposed in this trans during your SGD sessions. I hope we’re at least on the right track with our diagnosis and differentials, but there’s a chance our preceptors will point out something totally different. Hopefully that won’t be the case. The ‘answers’ to the questions are based solely on our research, and in anticipation of additional points we might have missed, there are boxes below each tentative answer so that you can fill in the blanks. Good luck on the exam, everyone!

I. The Case

General Data R. D. is a 26 year-old male, right-handed, single, born and residing in Manila, admitted for the chief compliant of unarousability History of the Present Illness The patient was apparently well and of good functional capacity until… 36 hours prior to admission, the patient had a drinking spree with friends consuming several bottles of brandy and several bottles of beer. After the binge, the patient went to sleep without eating his dinner. 24 hours prior to admission, the patient was noted to be unarousable despite vigorous verbal and tactile stimulation. The patient then had 1 episode of stiffening of both upper and lower extremities, with upward rolling of eyeballs, drooling of saliva, and involuntary micturition, lasting for approximately 20 seconds. The patient was then brought to a local hospital, where he was given 1 vial of D50-50 IV and 1 ampoule of Vitamin B complex IV. He was then transferred to PGH for further evaluation and management. Review of Systems Past Medical History o No other known illnesses or co-morbidities o No previous hospitalizations or surgeries

Family Medical History o (+) pulmonary tuberculosis (maternal), (+)

hypertension (father) o (-) asthma, heart disease, stroke

Personal and Social History o Regular alcoholic beverage drinker (2-4 sessions per

week) o Smoker: consumes 1 stick per day for 1 year o MAP user 1995-1996; not known if still presently

using shabu Physical Examination Findings o Received at the ER drowsy but arousable, not in

cardiorespiratory distress o BP120/80, HR 70/min, RR 20/min, T 37.2°C o Pink palpebral conjunctivae, anicteric sclerae, no

cervical lymphadenopathy, no jugular venous distention, no carotid bruit;

o (-) dental caries, (-) tonsillopharyngeal congestion o equal chest expansion, clear breath sounds, (-)

adventitious sounds o (-) heaves/thrills, apex beat at the 4th intercostal

space midclavicular line, normal heart rate and regular rhythm, (-) murmurs

o Flat abdomen, normoactive bowel sounds, soft, (-) masses/tenderness/organomegaly

o Full and equal pulses, pink nailbeds, o (-) Pallor/edema/cyanosis

Neurologic Examination Findings o Drowsy but arousable by tapping, no verbal output,

uncooperative, restless and does not follow commands

o Pupils 2-3 mm equal, briskly reactive o (+) ROR, clear media, (-) papilledema, (-) retinal

hemorrhages/exudates, o (-) preferential gaze, roving, conjugate eye

movements, o (+) brisk corneal reflexes, (-) facial asymmetry o (+) brisk gag reflex o unable to protrude tongue on command o (-) preferential movement o Withdraws to pain in all extremities o DTRs +++ in all extremities; (-) Babinski sign; (-)

clonus o (-) nuchal rigidity, (-)Brudzinski sign, (-) Kernig’s sign o (-)nystagmus, (-) tremors o (-)Horner syndrome

II. The Questions 1) Give a 3-sentence summary of the pertinent features of the case. The case features R.D., a 26 year old male who was well and of functional capacity until an evening of binge drinking 36 hours prior to admission. 24 hours prior to admission, the patient was found to be somnolent and unresponsive to verbal and tactile stimulation, with stiffening of the upper and lower extremities, upward rolling of the eyeballs and involuntary micturition. Physical examination showed no significant abnormalities and the neurologic examination findings were normal other than the patient’s episode of altered sensorium. Notes: 2) What neural structures are involved? What is your localization? Mamillary bodies - The mammillary bodies are parts of the brain known to be significantly damaged by alcohol intoxication, especially by chronic alcohol abuse and associated deficiency of thiamine. They, along with the anterior and dorsomedial nuclei in the thalamus, are involved with the processing of recognition memory. CN III, IV, VI – Damage to these cranial nerves which serve the extra-ocular muscles can explain the upward



Exam 1


Ikey and Lee

rolling of the eyes noted prior to R.D.’s admission. Thalamus - The thalamus plays an important role in regulating states of sleep and wakefulness. Thalamic nuclei have strong reciprocal connections with the cerebral cortex, forming thalamo-cortico-thalamic circuits that are believed to be involved with consciousness. The thalamus plays a major role in regulating arousal, the level of awareness, and activity. Damage to the thalamus can lead to permanent coma. Many different functions are linked to the system to which thalamic parts belong. This is at first the case for sensory systems (which excepts the olfactory function) auditory, somatic, visceral, gustatory and visual systems where localized lesions provoke particular sensory deficits. A major role of the thalamus is devoted to "motor" systems. This has been and continues to be a subject of interest for investigators.

Cerebellar Vermis - It is the site of termination of the spinocerebellar pathways that carry subconscious proprioception.

Recent research on the posterior cerebellar vermis indicates that this particular area of the brain may be linked to the brain's natural ability to integrate and analyze inertial motion. Specialized cells in this area, known as Purkinje cells, are now thought to receive sensory information from the vestibular system of the inner ears and use this to compute information about the body's movement through space.

Notes:

3) What is the etiology of the illness? What are the differential diagnoses?

Wernicke’s Encephalopathy – A syndrome characterised by ataxia, ophthalmoplegia, confusion, and impairment of short-term memory. It is caused by lesions in the medial thalamic nuclei, mammillary bodies, periaqueductal and periventricular brainstem nuclei, and superior cerebellar vermis, often resulting from inadequate intake or absorption of thiamine (Vitamin B1), especially in conjunction with carbohydrate ingestion. Its most common correlate is prolonged alcohol consumption resulting in thiamine deficiency. Alcoholics are therefore particularly at risk, but it may also occur with thiamine deficiency states arising from other causes, particularly in patients with such gastric disorders as carcinoma, chronic gastritis, and repetitive vomiting.

It should be noted that although Wernicke’s encephalopathy is defined by classic triad of symptoms (encephalopathy, ataxic gait, oculomotor dysfunction), all three features of the triad are observed in only about one-third of cases. Consideration for Wernicke encephalopathy should be given to patients with any

evidence of long-term alcohol abuse or malnutrition and any of the following: acute confusion, decreased conscious level, ataxia, ophthalmoplegia, memory disturbance, hypothermia with hypotension, and delirium tremens.

Long-term alcohol abuse is the most common cause of Wernicke encephalopathy. In long-term alcoholics, malnutrition can reduce intestinal thiamine absorption by 70%, decreasing serum levels of thiamine from between 30% and 98% below the lower level established for normal subjects. Alcohol alone can also decrease absorption by 50% in one third of patients who are not malnourished.

R/I: o Alcohol abuse (2-4 drinking sessions per week) o Oculomotor dysfunction o Altered sensorium o Ataxia (not entirely certain, but the stiffening of

extremities may correlate with an overall lack of coordination in muscle movements)

o An effective Vitamin B complex treatment would suggest improvement of possible thiamine deficient state

R/O:

o Does not directly explain involuntary micturition or drooling

o Stupor and coma are rare symptoms o No nystagmus o Usually does not present with seizure-like

symptoms Hypoglycemia due to excessive alcohol consumption (Note: for this differential, we found this abstract of a recently published study explaining the possible pathophysiology of alcohol-induced hypoglycemia) Hypoglycemia induced by alcohol ingestion is a well-known clinical problem in diabetic patients. However, the mechanisms underlying this phenomenon have largely remained elusive. Since insulin secretion can be rapidly tuned by changes in pancreatic microcirculation, scientists at the Stockholm South Hospital Diabetes Research Center, Karolinska Institutet, evaluated the influence of alcohol administration on pancreatic islet blood flow and dynamic changes in insulin secretion and blood sugar levels. "We have now found that alcohol exerts substantial influences on pancreatic microcirculation by evoking a massive redistribution of pancreatic blood flow from the exocrine into the endocrine (insulin-producing) part via mechanisms mediated by the messenger molecule nitric oxide and the vagus nerve, augmenting late phase insulin secretion, and thereby evoking hypoglycemia" says lead investigator Åke Sjöholm. In general, symptoms of hypoglycemia include hunger, nervousness, tremors, perspiration, sleepiness, confusion, difficulty speaking, generalized weakness, seizures and anxiety. R/I:

o Sleepiness o Excessive alcohol intake o Altered sensorium o Can cause single or multiple focal or generalized

seizures o Pt did not eat before drinking

R/O:

o Does not account for opthalmoplegia, ataxia



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Ikey and Lee

Stroke - Stroke should be considered in any patient presenting with an acute neurologic deficit (focal or global) or altered level of consciousness. Common symptoms of stroke include abrupt onset of hemiparesis, monoparesis, or quadriparesis; monocular or binocular visual loss; visual field deficits; diplopia; dysarthria; ataxia; vertigo; aphasia; or sudden decrease in the level of consciousness. R/I:

o Decreased level of consciousness o Ataxia (not entirely certain, but the stiffening of

extremities may correlate with an overall lack of coordination in muscle movements)

R/O:

o PE findings are not suggestive of stroke o No history of CV disease o No hemi/mono/quadriparesis o No strong correlation linking alcohol as a risk

factor for ischemic stroke. o No family history

Ethanol Intoxication SERUM LEVELS

(mg/dL) MANIFESTATIONS

50 – 150*

euphoria or dysphoria

shy or expansive

friendly or argumentative

impaired concentration and judgment

sexual inhibitions

150 – 250

slurred speech

ataxic gait

diplopia

nausea

tachycardia

drowsiness

labile mood with sudden bursts of anger or

antisocial acts

300

stupor alternating with combativeness or incoherent speech

heavy breathing

vomiting

400

coma

500 respiratory paralysis

death

R/I: o Stupor o Can cause seizures

R/O: o Cannot be ruled out completely but pattern of

symptoms suggest a more specific syndrome Epileptic seizure - An epileptic seizure is caused by excessive and/or hypersynchronous electrical neuronal activity, and is usually self-limiting. It can manifest as an alteration in mental state, tonic or clonic movements, convulsions, and various other psychic symptoms (such as déjà vu). This needs to be differentiated from epilepsy, which is the medical syndrome of recurrent, unprovoked seizures, but seizures can occur in people who do not have epilepsy.

Seizures are often associated with a sudden and involuntary contraction of a group of muscles and loss of consciousness. However, a seizure can also be as subtle as marching numbness of a part of the body, a brief - long term loss of memory, sparkling or flashes, sensing/discharging of an unpleasant odor similar to alcohol base is produced by internal organs, a strange epigastric sensation or a sensation of fear and total state of confusion which in some case leads to suicide during seizure. Other common symptoms of seizure include: chewing movements, difficulty talking, drooling, eyelid fluttering, eyes rolling up, falling down, hand waving, inability to move, incontinence, lip smacking, making sounds, staring, stiffening, twitching movements, breathing difficulty, sweating and teeth clenching.

Checking glucose levels, for example, is a mandatory action in the management of seizures as hypoglycemia may cause seizures, and failure to administer glucose would be harmful to the patient.

R/I: -Altered mental state, loss of consciousness -Drooling -Incontinence -Stiffening of extremities -Eyes rolling upwards R/O: -Often associated with concurrent cardiac or endocrine diseases Notes:



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Ikey and Lee

4) Based on your main working diagnosis, what is the pathophysiology of the signs and symptoms seen in this patient?

Epileptic seizure and altered sensorium induced by binge drinking, is the diagnosis which offers the most complete explanation for the patient’s symptoms. Seizures can be caused by sever hypoglycemia, and in this case there are two possible explanations for a hypoglycemic state. Firstly, after a night of binge drinking, the patient went to sleep with no additional food intake. A prolonged period of fasting can induce low blood sugar. Secondly, R.D. may have been functionally hypoglycemic, even if his blood sugar levels were normal, due to thiamine deficiency. Thiamine deficiency, common in patients suffering from alcohol abuse, affects the body’s ability to metabolize carbohydrates, so a lack of Vitamin B1 can induce a situation similar to actual hypoglycemia. Furthermore, as a general depressant of the nervous system, the state of unarousability described in the case can also be attributed to excessive alcohol intake.

The precipitating event in this case is excessive consumption of alcohol (ethanol). The presence of large amounts of ethanol has an adverse effect on the absorption of Vitamin B1 (thiamine). Acute alcohol exposure interferes with the absorption of thiamine from the gastrointestinal tract at low, but not at high, thiamine concentrations. Furthermore, in studies using rats, the activity of the TPK (thiamine diphosphokinase) enzyme from various tissues decreased with acute alcohol exposure to about 70 percent of the activity level in control animals, and with chronic alcohol exposure to about 50 percent. Although no studies have addressed whether alcohol directly affects TPK in humans, indirect analyses have found that the ratio of phosphorylated thiamine (primarily ThDP, the form utilized in cell metabolism) to thiamine is significantly lower in alcoholics than in nonalcoholics - that is, that less thiamine is converted to ThDP. This finding suggests that TPK is less active in the alcoholics.

Thiamine malabsorption could become clinically significant if combined with the reduced dietary thiamine intake that is typically found in alcoholics, when other aspects of thiamine utilization are compromised by alcohol, or when a person requires increased thiamine amounts because of his or her specific metabolism or condition (in pregnant or lactating women).

Thiamine in its metabolically active form, called thiamine pyrophosphate (TPP), is vital in the metabolism of carbohydrates. It serves a critical role in 3 enzyme systems: (1) conversion of pyruvate to acetyl coenzyme A by pyruvate dehydrogenase, (2) conversion of a-ketoglutarate to succinate by a-ketoglutarate dehydrogenase in the Krebs cycle, and (3) catalysis by transketolase in the pentose monophosphate shunt. In the presence of thiamine deficiency, these cellular systems dependent on thiamine begin to fail, leading eventually to cell death.

Diminished transketolase activity results in failure of the maintenance of the myelin sheaths in the nervous system, metabolism of lipids and glucose, and production of branched chain amino acids.

Lack of a-ketoglutarate dehydrogenase activity in the Krebs cycle alters cerebral energy utilization. If cells with high metabolic requirements have inadequate stores of thiamine to draw from, energy production drops, and

neuronal damage ensues. Increased cell death then feeds the localized vasogenic response (Buscaglia, 2005). Additionally, the reduced production of succinate, which plays a role in GABA metabolism and the electrical stimulation of neurons, leads to further CNS injury.

As for the pathophysiology of a seizure itself, two sets of changes can determine the epileptogenic properties of neuronal tissues. Abnormal neuronal excitability is thought to occur as a result of disruption of the depolarization and repolarization mechanisms of the cell (this is termed the "excitability of neuronal tissue"). Aberrant neuronal networks that develop abnormal synchronization of a group of neurons can result in the development and propagation of an epileptic seizure (this is termed the "synchronization of neuronal tissue").2

A hyperexcitability of neurons that results in random firing of cells, by itself, may not lead to propagation of an epileptic seizure. Indeed, both normal and abnormal patterns of behavior require a certain degree of synchronization of firing in a population of neurons. Epileptic seizures originate in a setting of both altered excitability and altered synchronization of neurons.

The membrane properties and microenvironment of neurons, which maintain potential differences of electrical charge, are determined by selective ion permeability and ionic pumps. Excitatory neurotransmitters usually act by opening Na+ or Ca2+ channels, whereas inhibitory neurotransmitters usually open K+ or Cl- channels. The mechanism of action of certain anticonvulsant medications is by Na+ or Ca2+ channel blockade, which likely prevents repetitive neuronal firing. Extracellular ionic concentrations also can contribute to neuronal excitability; for example, an increase in extracellular K+ concentrations (such as in rapid neuronal firing or dysfunction of glia, which are mainly responsible for K+ reuptake) causes membrane depolarization.

Various intracellular processes are controlled by genetic information. Neuronal excitability can be preprogrammed by DNA-controlled effects on cell structure, energy metabolism, receptor functions, transmitter release, and ionic channels. The mechanisms that induce these changes, either phasic or long-term, appear to be linked to ionic currents, especially Ca2+ influx. Intracellular Ca2+ mediates changes in membrane proteins to initiate transmitter release and ion channel opening; it also activates enzymes to allow neurons to cover or uncover receptor sites that alter neuronal sensitivity. Various plastic or persistent changes in excitability can result by influencing the expression of genetic information through Ca2+ influx. This may occur by selectively inducing genes to synthesize a protein for a specific reason. One example is the induction of the c-fos gene to produce c-fos protein in neurons involved in an epileptic seizure by the administration of pentylenetetrazol. The exact effects of this coupling are not known, but it provides a means to study the effects of neuronal excitation on cell growth and differentiation as a model for epilepsy, learning, and memory.

Notes:



Exam 1


Ikey and Lee

5) What diagnostic procedures are you going to facilitate for this patient?

o Blood Alcohol levels Alcohol toxicity can cause neural

symptoms and seizures o Blood Glucose

To rule out alcohol-induced hypoglycemia

o Thiamine levels Wernicke encephalopathy – low

thiamine levels Pt was already given B Complex – an

improvement supports a Dx of Wernicke’s encephalopathy

o Drug Screen Check if the patient still has MAP in his

system which can cause unpredictable results when mixed with ethanol

o CT Scan To check for focal lesions

6) What is the value of each of the diagnostic tests done on this patient? See Question 5 7) What are the initial approaches to therapy?

o Thiamine 100mg IV or IM Given daily until patient resumes a

normal diet Should be given prior to treatment with

IV glucose solutions o Glucose IV –

Standard treatment (along with Thiamine) for alcohol related toxicity.

Not to be given w/o Thiamine due to risk of precipitating or worsening Wernicke’s disease

8) What is the prognosis for this patient?

o Dependent on time before beginning treatment Untreated Wernicke’s can progress to

Korsakoff’s syndrome affecting memory Prolonged and severe hypoglycemia

can cause global insult to the neurons of the brain

GREETINGS: Ikey: Hello to the footballers of 2012 (championship #4, here we come!), to Lee (happy birthday), to Gillian, Kris, Ivan, Mean, Errol, Chard (for settling their accounts), to Raphy (for also settling his account and for writing the TRP song that’s going to win our class first place this year!), to Maddie and Adrian (for already paying part of the 2nd sem funds way ahead of schedule), to Barre (car-talk buddy), Nobel Neonates (get well soon, CO). Hello to Block B, good luck with GI! 5 weeks until Christmas break! Lee: Thanks for all the birthday greetings! Happy birthday to the fellow November celebrants: Jay, Mike Perez, Suzie, Nemo, Borgy, Alex, Noems, Jay-R, Diane, Butch, Laura, Kenneth, Gio, NiÑo, Aimee, Dane, Crystal, and Mitch (and any other Nov b-days I missed). Raphy et al, nice job on the TRP song! Congrats to Nobel Neonates on our successful weekend. Good luck to all our Palarong Med teams this weekend! Hi Lyz! To my Brods & Sisses, AFTG!

Notes:

Documents

Altered Sensorium SGD (Advanced Trans)