Clinical Scenarios
Rapidly progressive cognitive decline, startle myoclonus
What is Creutzfeldt-Jakob disease (prion disease)
Difficulties with concentration, memory, judgement. Depression, apathy and hypersomnia also common. Basal ganglia and cerebellar dysfunction manifest as ataxia, nystagmus and hypokinesia.
Dx: rapid progression with at least 2 of the following: myoclonus, visual/cerebellar signs, pyramidal or EPS signs, akinetic mutism.
List one common precipitant of delirium in children
febrile illness, medications
Found in the CSF of a patient with a neurocognitive disorder due to HIV
High viral loads
-History of severe immunosuppression, advanced HIV infection
Medication indicated for treatment of agitation in delirious patients
Haloperidol
Abnormal Mini Mental State Exam score cutoff
dysfunction: <25
A 74 yo man is brought to the office by his wife due to a change in behavior. Over the last year, the pt has had difficulty recognizing his grandchildren and has gotten lost in his local grocery store more than once. He enjoys playing Sudoku in the Sunday newspaper but has increasing difficulty completing the puzzles. He has also been increasingly distractible during conversation and says that he sometimes sees animals in the house despite the couple not owning any. The patient has not seen a doctor in >20 years and takes no meds. His wife says that he started “slowing down” and talking about stiffness and a tremor approximately 4 years ago, which was before he experienced any behavioral symptoms; they never sought medical care because they assumed it was “just part of getting older”. Exam shows intact cranial nerves as well as pinprick and light touch sensations. There is rigidity in the b/l upper and lower extremities that is worse on the left. Tremor is present in both hands at rest and is worse in the left hand. Movement and speech are slowed. Gait is unsteady and marked by a shortened stride. What is the most likely dx?
what is parkinson's disease
-progressive neurodegenerative disease, dopamine depletion in the basal ganglia
-Depression, apathy, personality changes are common. Psychotic symptoms can occur as a result of the treatment or from the disease itself.
-Dx: requires presence of bradykinesia and either tremor or rigidity.
-Txt: carbidopa-levodopa and/or dopamine agonists for motor symptoms. Cholinesterase inhbiyors to treat cognitive symptoms and even to treat neuropsych symptoms such as hallucinations.
Which type of delirium is more common in drug withdrawal or toxicity
hyperactive type "ICU psychosis". Agitation, mood lability, uncooperativeness.
-Three types of delirium:
1. Mixed type (most common): psychomotor activity fluctuates from baseline between hypo and hyperactivity
2. Hypoactive: more common in elderly, often goes undetected, drowsiness, lethargy, stupor
3. Hyperactive type
Chromosome number implicated in Huntington's disease
-CAG repeats in gene encoding the huntingtin (HTT) protein on chromosome 4. Autosomal dominant
-Clinical: triad of motor, cognitive + psychiatric symptoms. Cognitive and behavioral decline can precede motor signs by up to 15 years.
-Executive function primarily affected. Depression, apathy, irritability, impulsivity, hallucinations, paranoia.
-Chorea (jerky dance like movements) and bradykinesia
Class of medications that may help reduce disinhibition, anxiety, impulsivity in patients with Frontotemporal Degeneration
serotonergic medications (SSRIs, trazadone)
Hypertension, diabetes, smoking, afib are risk factors for what type of dementia in particular
Vascular cognitive impairment/disease
-accounts for 20% of major neurocognitive disorders.
-Stepwise deterioration in cognitive function
A 42 year old vegan presents with cognitive impairment, paresthesias, and diminished position and vibration sensation. What is the most likely diagnosis?
Vitamin B12 deficiency
Characterized by a fluctuating disturbance in ___ and ____.
attention and awareness
-Symptoms develop acutely over hours to days and fluctuate throughout the course of the day, tyically worse at night.
-Deficits include recent memory, language abnormalities or perceptual disturbances (visual hallucinations).
the epsilon-4 variant of what gene is a risk factor for developing early onset alzheimer's disease
apolipoprotein gene
-Accumulation of extraneuronal beta-amyloid plaques and intraneuronal tau protein tangles is associated with progressive brain atrophy
The mechanism of action of memantine
NMDA receptor antagonist.
-Other txt: cholinesterase inhibitors slow clinical deterioration by 6-12 months in 50% of mild to moderate AD.
"The combination of memantine and a cholinesterase inhibitor leads to modest improvements in cognition and global outcomes in patients with advanced disease" (uptodate)
Pronounced antipsychotic sensitivity is associated with Lewy Body disease or Parkinsons?
Lewy Body
-Antipsychotic agents have limited efficacy in patients with dementia in general and in DLB in particular
-Associated with the potential for severe sensitivity reactions, including exacerbation of parkinsonism, confusion, or autonomic dysfunction
waxing and waning cognition, visual hallucinations, development of Parkinsonian features 1 year after cognitive decline and ___ are core features of Lewy Body Disease
REM sleep behavior disorder. Violent movements during sleep in response to dreams, often of fighting.
-Lack of muscle atonia during REM sleep. More often in second half of sleep episode.
-txt: clonazepam. However remember that benzodiazepines are generally avoided (except for REM sleep disorder), especially for long-term use, because of the potential for worsening confusion, gait disorder, and paradoxic agitation. (UpToDate)
What should you consider doing if a patient with delirium presents with: 1. no evident underlying cause 2. new focal neurologic deficits on exam 3. patient unwilling to cooperate with a neurologic exam 3. No improvement despite treatment of already identified causes
Consider obtaining a head CT
Type of aggregations found in the brains patients with lewy body disease
alpha-synuclein
List one symptom directed therapy for Huntington's Disease
tetrabenazine or atypical antipsychotics
What intervention can result in clinical improvement of normal pressure hydrocephalus
CSF removal via lumbar puncture
-"wet, wobbly, wacky"
-ventriculoperitoneal shunt may also improve symptoms
A 64-year-old woman is brought to the emergency
department by her neighbor, who says “ my friend isn’t acting right.” The patient requires the support of nurse while walking to an examination table. Examination reveals that she cannot correctly identify the season or the town she is in. She does not recognize her neighbor. She is inattentive and seemingly apathetic to the activity round her. She dozes off repeatedly during the interview, but each time is arousable and resumes answering questions. Her answers are illogical and inconsistent.
Vital signs are within normal limits and she is neither tremulous nor diaphoretic. Neurologic examination finds bilateral sixth nerve palsy and horizontal nystagmus. Urine toxicology screen and blood alcohol level are negative.
Wernicke Encephalopathy
-B1 thiamine deficiency
-Ataxia, confusion, ocular abnormalities (nystagmus, gaze palsies)
Name for new onset agitation and confusion in the setting of benzodiazepine use. (uncommon)
paradoxical agitation, <1%
- Txt: stop benzo use
In what disease is CSF positive for 14-3-3 proteins
CJD
Part of the CJD diagnosis requires supportive findings from at least one diagnostic modality, also including:
-periodic sharp wave complexes on EEG
-lesions in the putamen or caudate nucleus
What agents are associated with increased mortality in patients with dementia
antipsychotics
An indicative biomarker in Lewy Body Dementia includes decreased ___ uptake on myocardial scintigraphy.
123iodine-MIBG
123-I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy demonstrates low uptake in DLB, representing reduced postganglionic sympathetic cardiac innervation. In small series, this test appears to have high sensitivity and specificity for DLB, especially when distinguishing it from AD. MIBG myocardial scintigraphy might detect early disturbances of the sympathetic nervous system in DLB (uptodate)