Unilateral Fixed Dilated Pupil - Differential Diagnosis Framework
If Altered Mental Status - Consider Oculomotor (3rd cranial nerve) Palsy:
• Brain (uncal) herniation, lntracranial hypertension, lntracranial hemorrhage, SAH, tumor
• Posterior communicating artery aneurysm (Compression)
If no neurological cause, consider:
• Trauma
• Medication effects
• Congenital abnormalities
#Unilateral #Fixed #Dilated #Pupil #differential #diagnosis #neurology
Transverse Myelitis Overview
Focal inflammatory disorder of the spinal cord resulting in rapid onset of weakness, sensory alterations, and bowel or bladder dysfunction
Epidemiology:
• 1400 new cases in the US each year
• Bimodal peaks between the ages of 10 to 19 years and 30 to 39 years
• 10-33% develop MS over a five to ten-year period
• 75-90% of cases TM is monophasic
Pathophysiology of Transverse Myelitis:
• Excessive activation of an immune response against the spinal cord that results in CNS inflammation and tissue damage
Mechanisms:
• Idiopathic: etiology unknown
• Infectious: Direct microbial infection versus molecular mimicry or super-antigen mediated disease
• Immune Mediated
Transverse Myelitis - Clinical Presentation:
Injury to the spinal cord (Myelopathy) without cord compression (MRI) and findings of varying degrees of:
1. Weakness:
- Weakness that preferentially affects the flexors of the legs and the extensors of the arms (pyramidal distribution of weakness)
- Flaccidity -> Spasticity
- Reflexes: decreased or absent initially -> Hyperreflexia develops later
2. Sensory Alterations:
- Sensory features: paresthesias ascending from feet with or without back pain at/near level of myelitis
3. Autonomic Dysfunction:
- Autonomic: Bowel/Bladder dysfunction, temperature dysregulation, bouts of HTN
Diagnostic Criteria:
• Sensory, motor, or autonomic dysfunction located at the spinal cord
• T2 hyperintense signal change on spinal MRI
• No evidence of compressive cord lesion
• Bilateral signs and/or symptoms
• Clearly defined sensory level
• CSF inflammation: CSF pleocytosis, elevated IgG index
• Progression hours to days
Transverse Myelitis Diagnosis:
• Must rule out compressive myelopathies!
• Gadolinium-enhanced MRI of the spinal cord
- Increased T2 signal and expansion of the cord
- No cord compression
- More than 2/3 of the cross-sectional area is involved
- Focal enlargement
- T2WI hyperintensity
- Enhancement
- TM and tumor the cord is swollen, while in MS and ADEM the cord is not swollen or less swollen
- Lesion > 3 levels: Evaluate for NMO, SLE or Sjogren's
• CSF:
- Abnormal in 50% of cases
- Pleocytosis: Mild lymphocytic
- Pleocytosis > 100 cells: consider infectious myelitis
- Elevated IgG index
- Oligoclonal IgG bands (85 to 95% Predictive of MS)
• Check Vitamin B12 and copper levels
• NMO-IgG (anti-AQP4) should be tested and if negative, MOG-IgG test should be ordered
• Infectious causes need to be ruled out
• Brain MRI: Check for brain and/or optic nerve lesions suggestive of multiple sclerosis, NMOSD, MOG antibody disorders, or ADEM
Transverse Myelitis Etiologies:
• Demyelination:
- Multiple sclerosis (MS)
- Neuromyelitis optica (NMO)
- Idiopathic transverse myelitis
- ADEM
- Post vaccination
- Myelin oligodendrocyte glycoprotein (MOG) antibody disorders
• Infections:
- Herpes zoster, West Nile virus
- Herpes simplex virus, HIV, Hep A/B/CMV, TB
- Treponema Pallidum
- Lyme Disease Mycoplasma
- Leptospirosis, Brucellosis
- Dengue, EBV, Influenza, Enteroviruses
• Idiopathic:
- Post Infectious
- Post Vaccine
• Inflammatory Disorders:
- SLE
- Neurosarcoidosis
- MCTD
- Bechet disease
- Sjogren
- Vasculitis- Heroin
• Paraneoplastic:
- AntiGAD65, NMDAR, AntiCRMP IgG, Anti-Hu
- Antiamphiphysin antibodies
• Nutritional Deficiency:
- Vitamin B12, E, D, copper
Transverse Myelitis Treatment:
• Steroids
• Plasma exchange
• Immunomodulatory agents: IVIG
• Cyclophosphamide
#Transverse #Myelitis #diagnosis #management #neurology #differential
Tinnitus - Subjective (heard only by patient) - 90% - Differential Diagnosis Algorithm
Unilateral On Audiogram - Perform MRI to rule out RC Lesion
• Acoustic Neuroma
• Lesion of Cochlear or Auditory Nerve
• Brainstem Lesion
• Multiple Sclerosis
• Infarction
• Méniére's Disease
Bilateral - No Hearing Loss:
• Metabolic Causes: Thyroid Dysfunction, Vitamin A, B, Zinc Deficiency.
• Psychogenic, Anxiety, Depression
• Drugs (Salicyclates, Quinidine, Indomethacin)
• Idiopathic
Bilateral - Conductive Hearing Loss:
• Lesion of External or Middle Ear
• Impacted Cerumen
• Otitis Media
• Otosclerosis
Bilateral - Sensorineural Hearing Loss:
• Noise Induced
• Ototoxicity
• Presbycusis
• Drugs (Propranolol, Levodopa, Loop Diuretics)
• Congenital
Somatic:
• TMJ
• Bruxism
• Whiplash
• Skull Fracture
• Closed Head Injury
#Tinnitus #Ringing #hearing #subjective #Differential #Diagnosis #Algorithm #Causes
Thiamine Deficiency - Differential Diagnosis Framework and Clinical Manifestations
Causes of Thiamine Deficiency:
• Poor intake:
- Diets high in polished rice/processed grains
- Chronic alcoholism
- TPN
- Gastric bypass surgery
• Poor absorption:
- Malnutrition
- Gastric bypass surgery
- Malabsorption
• Increased loss:
- Diarrhea
- Hyperemesis gravidarum
- Diuretic use
- Renal replacement therapy
• Increased thiamine utilization:
- Pregnancy
- Lactation
- Hyperthyroidism
- Refeeding syndrome
Sources of Thiamine:
• Found in: Yeast, Legumes, Pork, Brown rice, Cereals
• Low in: White/polished rice, Milled white cereals, Milk products
Thiamine
• Necessary For:
- Oxidative phosphorylation
- Myocardial energy production
• Deficiency leads to increased pyruvate and lactate
• Increased pyruvate & lactate decrease PVR and increase venous blood flow, increasing cardiac preload
• Increased preload and myocardial dysfunction leads to congestive heart failure
• Wet beri-beri triggers Right HF
• Moderate pulmonary HTN is common
• Hyperkinetic LVEF is also seen
• Lactic acidosis may not demonstrate diminished pH due to compensatory hyperventilation
Wernicke-Korsakoff Syndrome:
• Wernicke's Encephalopathy - Acute neurological condition:
- Nystagmus
- Ophthalmoplegia
- Ataxia/confusion
- WE + memory loss & psychosis with confabulation is consistent with WKS
• Korsakoff Syndrome - Chronic neurological condition:
- Impaired short-term memory
- Confabulation
Beri Beri:
• Dry Beri Beri:
- Symmetrical peripheral neuropathy of the distal extremities
- Sensory and motor impairments
- Impaired reflexes
- Burning pain in extremities
- Muscle weakness
- Falls due to peripheral neuropathy
• Wet Beri Beri:
- High output heart failure
- Dilated cardiomyopathy
- Tachycardia
- High output congestive HF
- Peripheral edema
Additional Findings:
• Acute renal failure:
- Increased Lactate/Pyruvate
- AV shunt, renal vascular contraction, blood flow reduction
- Decreased GFR
• Acute liver failure: Hepatic congestion due to RHF
#Thiamine #Deficiency #Manifestations #Differential #Diagnosis #syndromes #beriberi #nutrition #pathophysiology #wernickes #korsakoff
Syncope in 3 Steps
1. Consider the 3 "S" Mimics: Seizure, low Sugar, Stroke (TIA)
2. Heart vs SVR
Heart
• Pump > AS, HOCM, PE, pHTN, Tamponade
• Fluid > low like Gl loss, shunting like subclavian steal syndrome
• Rhythm > fast or slow
SVR
• Too much para > vasovagal, situational, carotid hypersensitivity and others <3
• Too little sympa > meds, diabetes, Parkinson (+), AL amyloidosis and other
#Syncope #differential #diagnosis #mimics
Stiff Person Syndrome (SPS) - Diagnosis and Management Summary
Epidemiology:
• Prevalence: 1-2 cases per million - rare
• Age 20-50, Females 2-3 times than men
• Commonly associated with DM-1, thyroiditis, vitiligo, and pernicious anemia
Stiff Person Syndrome Pathophysiology:
• Associated with autoimmunity
• Research indicates that it is the result of an autoimmune response gone awry in the brain and spinal cord.
Clinical Manifestations of Stiff Person Syndrome:
• Progressive muscle stiffness, rigidity, spasm - axial muscles
• Severely impaired ambulation
• Excessive muscle rigidity - lumbar, trunk, proximal muscles - sustained muscle contractions (agonist and antagonist muscles)
• Wide based gait with tendency to fall
• Triggers - sudden movement, noise, emotional upset
• Spasms - visualized-tight, rock-hard, board-like feel
• Autonomic dysfunction - hyperpyrexia, diaphoresis, high HR
• Sudden death - diaphragm spasm - apnea
Stiff Person Syndrome - Diagnosis:
• High index of suspicion
• Presence of:
- Stiffness in axial and limb muscles resulting in impairment of ambulation
- Presence of superimposed spasms triggered by noise, movement or emotions
- A positive therapeutic response to diazepam or findings of continuous motor unit activity on EMG
- Absence of other neurological disorders
• Testing anti-GAD (positive in 2/3 of pts)
• Therapeutic trial of diazepam
• EMG testing
Lab Findings in Stiff Person Syndrome:
• Anti-GAD Ab (>1000u/ml)
- People with SPS have elevated levels of GAD, an antibody that works against an enzyme involved in the synthesis of an important neurotransmitter in the brain.
• CSF: Oligoclonal bands
• Normal ESR, CRP
• Other autoantibodies - TPO, TTG, etc
EMG Studies:
• Continuous motor-unit activity, typically decreased by diazepam, sleep
DDx:
• Neuromyotonia, Tetanus, Strychnine poisoning, Parkinson's disease, Multiple sclerosis, Ankylosing spondylitis, Axial dystonia, Focal limb or joint disorders, Fibromyalgia, Psychosomatic illness, Anxiety, Phobia
Stiff Person Syndrome Treatment:
• Initial/Symptomatic Therapy:
- BDZ: Diazepam or clonazepam
• Resistant to Initial Symptomatic Therapy:
- Baclofen
• Severe Disease/Resistant:
- IVIG
- If Resistant to IVIG: Rituximab (anti-CD20), plasma exchange, or others (botox, sodium valproate, vigabatrin, propofol)
#Stiff #Person #Syndrome #SPS #Diagnosis #Management #treatment #neurology
Pupils: Localization in Coma
• Small, Reactive pupils: Metabolic coma.
• Unilateral Fixed, dilated pupil : uncal herniation, PCOM aneurysm.
• Bilateral, Large fixed pupils: Midbrain lesion or Death.
• Bilateral, midposition, fixed pupils: Transtentorial herniation.
• Pinpoint pupils: Pontine ICH, infarct, Opiate poisoning.
• Horner's syndrome: sympathetic dysfunction.
#Pupils #Localization #Coma #Neurology #differential #diagnosis
Posterior Reversible Encephalopathy Syndrome (PRES) Overview
Clinico-Radiological Syndrome, characterized by:
• Headache
• Seizures
• Altered mental status
• Visual disturbance
• White matter vasogenic edema affecting the posterior occipital and parietal lobes of the brain
PRES Clinical Presentation:
• Altered mental status
• Headache
• Seizures
• Vision changes
• Hypertensive crisis may precede the neurologic syndrome by 24 hours or longer/BP fluctuations
PRES-Associated Clinical Conditions:
• Preeclampsia, Eclampsia, Infection/Sepsis/Shock, Autoimmune disease, Cancer chemotherapy, Immunosuppressive agents, Renal failure, Transplantation including bone marrow or stem cell transplantation, Hypertension/Hypertensive emergency, Blood transfusion, Hypercalcemia
Etiology:
• Pathophysiology remains unclear, endothelial dysfunction is key, with hypertension being the most common precipitating factor
PRES Diagnosis:
1. Neurological symptoms: Acute onset
2. Risk factors
3. Imaging Patterns in PRES:
• Increased signal on T2-weighted images
• Vasogenic edema visualized as a hypo- or isointense signal on DWI
• White matter edema - both posterior cerebral hemispheres
• (FLAIR) sequences improve sensitivity showing cortical lesions
• Vascular narrowing on MRA/CTA
• Anterior circulation: MCA ACA watershed territories signal changes
4. Reversible course
Differential Diagnosis:
• Infection, Electrolyte abnormality, Medication/Drug toxicity, Metabolic disturbance, External lines/devices, Constipation, Seizures, Stroke, Paraneoplastic syndrome, ADEM, Acute toxic leukoencephalopathy, Cerebral venous thrombosis
Testing:
• Imaging: White matter vasogenic edema affecting the posterior occipital and parietal lobes of the brain
• CSF: Modestly elevated protein level (mean 58 mg/dL in one study) but no pleocytosis. An elevated white blood cell count in the CSF should prompt consideration of other diagnoses.
• EEG: With persistent altered level of consciousness to exclude nonconvulsive status epilepticus
Treatment:
• Address the underlying cause
• Treatment of HTN is the mainstay of therapy in patients
- 10-25% BP reduction initially, Avoid overaggressive BP lowering
- Lower the diastolic pressure to 100-105 mmHg within 2 to 6 hours
- Use easily titratable parenteral agents: clevidipine, nicardipine, or labetalol.
• Magnesium correction: Levels 2-3 mEq/L
• Seizures: Treat with AEDs until cause identified
#PRES #Posterior #Reversible #Encephalopathy #Syndrome #diagnosis #management #neurology
Photophobia and Headache - Differential Diagnosis Framework
Why?
• The coexistence of photophobia and headache suggests the potential reciprocal interactions between visual and pain pathways.
• Interactions between visual and pain pathways occur at the retina, midbrain, thalamus, hypothalamus, and visual cortex.
• In migraines: photophobia could result from photic activation of retina-driven pathways involved in the regulation of homeostasis.
Primary headaches:
• Migraine:
- 80 percent of people who have migraines have photophobia
- Bilateral photophobia
- Severe persistent photophobia
- Migraine with aura > migraine without aura
- Chronic migraine > episodic migraine
- Benign episodic mydriasis, miosis
• Tension-type headache:
- Bilateral or unilateral photophobia
- Mild persistent photophobia
• Trigeminal autonomic cephalalgias (TACs):
- Hemicrania continua, SUNCT, SUNA, etc.
- Unilateral
- Reversible, only during their cluster period
- Moderate, between migraine and tension-type headache
- Autonomic symptoms
- Miosis
Secondary headaches:
• Traumatic brain injury (TBI):
- Reversible or persistent photophobia
• Meningitis:
- Patients tend to have meningeal irritation signs
- Photophobia in viral meningitis is the most common form
• Non-traumatic subarachnoid hemorrhage (SAH):
- Mydriasis
- Can have isolated photophobia without headache
• Disorder of the eyes - Photophobia often precedes the onset of headache:
- Acute angle-closure glaucoma
- Ocular inflammatory disorder
- Trochlear headache
• CNS Vasculitis
Painful cranial neuropathies:
• Trigeminal neuralgia:
- Common in patients with the first division of the trigeminal nerve pain
- Mydriasis
• Painful optic neuritis
#Photophobia #Headache #differential #diagnosis #ophthalmology #Neurology