“WHITEOUT” DISEASE

DR. NARESH MULLAGURI, MDRESIDENT PHYSICIAN PGY2DEPARTMENT OF NEUROLOGYUNIVERSITY OF MISSOURI

HISTORY OF PRESENT ILLNESS

• Chief complaint: Altered mental status

• HPI: Respondent: Patient’s ex-wife

“My husband was fine until July 25 th as he was texting, driving and doing all his ADLs and IADLs by himself and I received a call from the Police Department on July 26 th, 2014 because her ex-husband was confused, disoriented, wandering around, trying to enter other people’s cars at Kohl’s departmental store.” At the time, patient could remember the ex-wife’s name and number but not the events that occurred prior to his confusion and he was sent to the South County regional Hospital where a CT scan of the head was performed which was unremarkable. The patient was discharged to home and left the hospital in a taxi. By the evening, patient did not reach home and he was found wandering again, walking around without his shoes on and the police department again contacted the ex-wife and she took him back to the South County regional Hospital And however he was released to his niece. The patient spent the next couple of days with his niece in Jefferson City and on the third day, the niece contacted patients ex-wife at night stating that the patient was confused, got lost at the store and couldn’t do activities of daily living, had urinary incontinence and somehow got into her car and drove away. He was found wandering around the next day in the morning in Rolla, Missouri by the police department. The patient at that time was able to remember the ex-wife’s name was oriented to self according to the report that could not have anything short of regarding the events that had happened. The patient was admitted to the hospital and managed for possible Wernicke’s encephalopathy based on patients prior history of heavy alcohol consumption. As he didn’t get better with the treatment, was transferred Calloway community Hospital in Fulton, Missouri on August 9, 2014 for the management back and a contrast CT scan of the head was done which showed hyper density in the right parietal zone, suspicious for a mass and was transferred to the hospital on August 14, 2014 for further evaluation and management of his altered mental status.

Patient responds to questions minimally and said no to review of systems and was able to tell his name, ex-wife’s name and his PCP name. Follow simple one step commands.

HPI CONTINUED…

Past Medical History:

• Migraine headaches

• Hypertension

• Hypothyroidism

• Sleep apnea on CPAP

• Anxiety and Depression

• Cervical spine degenerative disc disease

• Hypertriglyceridemia

• Benign prosthetic hypertrophy

• Gastro-esophageal reflux disease

Past surgical history:

• Hernia repair in 1981

• Multiple faucet injections in the left C2-C3 Junction in 2012

Home medications:• Levothyroxine 75 µg daily• Aspirin 81 mg daily• Lamictal 200 mg once daily• Vistaril 25 mg 3 times a day when necessary for anxiety• Metoprolol 25 mg twice a day• Tadalafil 5 mg once a day• Fish oil twice a day• Alprazolam 0.5 mg at bedtime when necessary for insomnia.• Multivitamin once daily• Hydroxyzine 50 mg twice a day• Omeprazole 20 mg daily• Percocet 10 mg 4 times a day• Cymbalta 60 mg once a day

HPI continued…Family and social history:• Father: 77 years old, living had history of myocardial infarction, motor vehicle accident

sustained brain injury

• Mother deceased at the age of 56 had diabetes and myocardial infarction

• Separated, chronic alcohol with reports of heavy consumption, DAILY SNUFF, never used illicit drugs

• Used to work as a truck driver for the Oil company.

PHYSICAL EXAMINATIONVitals:

Temperature: 37*C

Pulse Rate: 97

Respiratory rate: 20

Blood Pressure: 117/78 mm of Hg

General: Patient is lying comfortably on the hospital bed uninterested in surroundings, not interacting with things, doesn’t establish eye contact during conversation.

Eyes: No pallor or icterus, didn’t look to the sides on command but able to roll his eyes to his left and right spontaneously.

HEENT: Normocephalic and atraumatic, oral cavity is moist with normal palate, posterior pharyngeal wall and tonsillar pillars. Dentition is intact. No tongue bite.

Neck: Stiff more in the flexion and extension movements and some to lateral motion, velocity dependent, trachea is in midline and no palpable thyromegaly

Cardiovascular: Regular rate and rhythm, no murmurs, S1 and S2 heard in all the areas.

Respiratory: Coarse breath sounds bilaterally

Gastrointestinal: soft, no tenderness, no palpable organomegaly and bowel sounds are present in all the quadrants.

Extremities: No pedal edema, joint effusions or tenderness, Peripheral pulses were palpable.

PHYSICAL EXAMINATION CONTINUED…

Musculoskeletal: No stiffness appreciated, Preserved range of motion in all the extremities.

Neurological exam: Higher mental functions:

Patient is awake, alert and oriented person, date of birth. Attention and concentration are poor. Memory is impaired to recent and remote events. Registration is poor as well as recall. Naming, reading and writing were severely impaired. Able to repeat some sentences and perseverates his prior office address. Responded to most of the questions by nodding the head. Able to follow one step commands. He seems uninterested in surroundings and not interacting with the things like television remote. Unable to understand both written and spoken commands other than gripping fingers, moving his toes, unable to feed himself but able to close the lips when the spoon is kept close to the mouth, Unable to open the coke tin by himself. No frontal release signs. Impaired Graphesthesia and stereognosis. Emotional incontinence (bursts of crying spells)

Cranial Nerve examination:

Visual field is intact in all the quadrants elicited through blink reflex, Able to spontaneously move his eyeballs in all the directions but didn’t track the finger while eliciting smooth pursuit, Pupils were round, equal and reacting to light bilaterally, No ptosis, corneal reflex is intact bilaterally, Brisk jaw jerk, No facial asymmetry and grimaces to painful supraorbital pressure bilaterally, Tongue is midline along with uvula and elevates symmetrically. No choking on drinking water or swallowing food, No dysphonia, Able to move his neck in both the directions, Shoulder shrug is strong bilaterally.

NEUROLOGICAL EXAMINATION CONTINUED…

Motor system examination:

Bulk: is equal in bilateral upper and lower extremities

Tone: Increased in all the extremities. In the upper extremities, more in the flexors and in the lower extremities, more in the extensors.

Power: Weakness in all the 4 extremities, 4/5 in all the extremities.

Deep Tendon Reflexes: 3+/4 in bilateral biceps, brachioradialis, triceps, pectoral jerks, knees and 4/4 in bilateral ankles with ill sustained clonus.

Plantars were up going bilaterally

Coordination: No tremors or truncal ataxia noticed. He didn’t perform finger to nose test or heel to shin test for me.

Cannot walk on his own but able to walk with widebase when assisted by the physical therapist initially but stiffness was an issue later, so he was unable to walk even with full asssistance.

Sensory system examination:Intact to pain in all the four extremities. Temperature, vibration and proprioception were not assessed.

DIFFERENTIAL DIAGNOSIS

• CNS infection including HIV

• Toxic metabolic Encephalopathy – The differential can be broad but I would put my money on Alcohol and Drugs right now though I will keep paraneoplastic and autoimmune in the differential.

• Subacute cerebritis

• Neurodegenerative diseases like FTD

LABS• WBC: 10.7(61%PMNs and 27%Lymphocytes)

• Hgb: 14.6

• HCT: 42.9%

• MCV: 85

• PLT: 280

• ESR: 37

• Urine drug screen in the outside hospital is negative except for Benzos and Opiates

• Na+: 137

• K+: 3.8

• Cl-: 98

• CO2: 28

• Anion gap: 15

• Glucose: 112

• BUN: 19

• Creatinine: 0.92

• Calcium: 9.6

• AST: 51

• ALT: 44

• ALP: 63

• T.Bili: 0.7

DIGGING CONTINUES…• B12: 636

• Folate: 28

• Vit-D: 35

• TSH: 4.2, in the OSH a month earlier it is 6.5, started Levothyroxine there.

• Free Thyroxine: 1.34

• Vitamin B1: 223

• Vit B6: 60

What do you want to order..?

AT 1 METER DEPTH OF DIGGING…AMINES/STIMULANTS: ANTIDEPRESSANTS: ANALGESICS:Amphetamine Amitriptyline Acetaminophen Methamphetamine Nortripyline Salicylate Caffeine ImipramineEphedrine Desipramine MISCELLANEOUS:Chlorpheniramine Doxepin PhencyclidinePhenylpropanolamine Amoxapine Cannabinoids Loxapine AlcoholBARBITURATES: Trazodone NicotineAmobarbital Cyclobenazprine StrychninePentobarbital QuinineButalbital SEDATIVES/HYPNOTICS: Trimethoprim Secobarbital Chlordiazepoxide Terpin Hydrate Phenobarbital Diazepam Flurazepam CARDIACS: NARCOTICS: Diphenhydramine LidocaineMorphine Meprobamate ProcainamideCodeine Phenothiazines QuinidineMeperidine HydroxyzinePentazocine Carisoprodol ANTICONVULSANTS:Methadone Alprazolam CarbamazepineOxycodone Gluthethimide PhenytoinHydrocodone Temazepam PrimidonePropoxphyene Lorazepam Hydromorphone Doxylamine

AT 1MILE INTO DIGGING….• Phosphorous: 4.8

• UA: -ve

• UDS and CDS: Hydroxyzine and cetirizine

• Manganese, Arsenic, Lead, Mercury – Normal

• Copper : 169 (70-140). Normal copper excertion and negative ceruloplasmin

• CSF

• Protein : 72 and 69

• Glucose : 55 and 79

• Lactic acid: 1.5 and 4.0

• WBC: 0 and 0

• RBC: 450 and 0

• Oligoclonal bands: 0

• IgG index – Normal

• MBP: 30.5(0-5.5)

• cryto – negative, AFB and Fungal cultures – Negative

• CSF bacterial culture – coagulase negative staphylococcus

• HIV – Negative

• Thyroglobulin: 19 with negative TPO

• ANA and paraneoplastic panel – negative

LETS SEE PICTURES….MRI OF THE BRAIN ON 08/15/2014 read by Dr. Ajay Agarwal, MD

Diffuse bilateral white matter diffusion restriction is seen without corresponding hypointense ADC mapping. Bilateral confluent T2/FLAIR hyperintense white matter lesions. A tiny foci of increased FLAIR signal is present within Right basal ganglia. On post contrast imaging, there is no suspicious enhancement. Midline structures including corpus callosum, pituitary, posterior fossa structures were unremarkable. Primary consideration is Toxic, metabolic encephalopathy, HIV related Encepahlopathy or SSPE.

MRI OF THE CERVICAL SPINE:

Moderate to severe multilevel cervical discogenic degenerative disease greatest at C3-C4 and C4-C5 with moderate central canal stenosis and narrowing of the left C4-C5 neuroforamina. No abnormal cord signal or post contrast enhancement.

PAN CT SCAN: suspicious for renal mass which was ruled out by renal ultrasound

CT ANGIOGRAPHY OF THE HEAD AND NECK is negative for any vasculitis or significant stenosis.

CT of the Head from 08/13/2014

MRI OF THE BRAIN – DWI SEQUENCE

EEG X 3 INCLUDING A 24 HR MONITORING• Low to medium amplitude mixture of theta and delta frequencies in the occipital region

with no stage 2 sleep. No spike and wave pattern or ongong epileptiform activity. Photic stimulation evoked driving response in the occipital region. Awake sustained alpha rhythm was not noted.

• Findings consistent with moderate to severe diffuse encephalopathy.

Dr. Sivaraman, MD and Dr. Bandyopadhyay, MD PhD

• Brain Biopsy report: Dr. Douglas Miller, MD

DEMYELINATING DISORDER

THOUGHT PROCESS • WERNICKE’S ENCEPHALOPATHY

• MARCHIAFAVA – BIGNAMI SYNDROME

• STEROID RESPONSIVE ENCEPHALOPATHY ASSOCIATED WITH AUTOIMMUNE THYROIDITIS (SREAT)

• TOXIC METABOLIC ENCEPHALOPATHY

• OPIATE INDUCED LEUKOENCEPHALOPATHY

• DEMYELINATING DISEASE

CLINICAL DIAGNOSIS

• TOXIC METABOLIC LEUKOENCEPHALOPATHY

OPIATE INDUCED LEUKOENCEPHALOPATHY

OPIATE INDUCED LEUKOENCEPHALOPATHY• Usually causes spongiform lesions in the white matter and case reports demonstrated

that cerebellar involvement is more common as kappa receptor density is more (speculation). Lactic acid levels will be increased as aerobic metabolism is shut down due to dysfunction of Mitochondria.

• Very rare cases of Demyelinating changes have been reported by some chinese studies.

• Heroin pyrosylate, Methadone and Oxycodone

have been known to cause these lesions. Usually

Confluent and necrotizing white matter lesions.

I AM HAPPY TO PRESENT THIS SLIDE

Thanks to my beloved faculty

• Dr. Munish Goyal, MD – For the wonderful Pizza talk and provided the literature Dr. Chuquilin, MD – My mentor for digging and finding the articles for me.

• Dr. Shenker, MD, PhD, the pioneer of this digging process and for accepting this patient as it provided us a good learning opportunity… When a Psychiatrist call you and say I have a patient with possibly no psychiatric causes and may need a Neurological evaluation – Don’t wait to accept.

• Dr. Burger, MD for taking the decision to get the Brain biopsy

• Dr. Miller, MD for Neuropathological microscopic examination.