A 20-year-old male with seizures. Give differentials.

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Differentials for Seizures in a 20-Year-Old Male

The first step is classifying the seizure as provoked (caused by an acute, reversible condition) or unprovoked (no identifiable acute precipitant). Provoked seizures account for nearly half of all first seizures. An epilepsy diagnosis requires two or more unprovoked seizures, or one unprovoked seizure with >60% risk of recurrence. - Frameworks for Internal Medicine, p. 559

UNPROVOKED SEIZURES (Epilepsy)

This is the most common category in a healthy young male.

Epilepsy Syndrome	Key Features
Juvenile Myoclonic Epilepsy (JME)	Onset 12-18 years; morning myoclonic jerks, tonic-clonic seizures, absence seizures; precipitated by sleep deprivation
Juvenile Absence Epilepsy	Staring spells lasting up to 10 sec; absence reproduced by hyperventilation; generalized 3 Hz spike-wave on EEG
Idiopathic Generalized Epilepsy	No structural cause; genetic basis; normal MRI
Benign Rolandic Epilepsy	Typically remits by late adolescence but may persist
Temporal Lobe Epilepsy (focal)	Aura (deja vu, epigastric rising, fear), automatisms (lip smacking, hand picking)
Frontal Lobe Epilepsy (focal)	Brief, nocturnal, hypermotor seizures; often misdiagnosed as psychogenic

In most cases, epilepsy is either genetic (a known mutation) or idiopathic (likely undiscovered genetic cause). - Frameworks for Internal Medicine, p. 558

PROVOKED SEIZURES

1. VASCULAR

Cerebral Venous Thrombosis (CVT) - Important in young adults, especially if on OCP use or dehydrated; seizure on presentation in ~50% of patients
Arteriovenous Malformation (AVM) - Congenital; classic cause of first seizure in young adults
Cavernous Malformation - Associated with recurrent focal seizures due to hemosiderin deposition
Subarachnoid Hemorrhage - "Worst headache of life" + seizure; aneurysm rupture
Posterior Reversible Encephalopathy Syndrome (PRES) - Associated with hypertension; generalized tonic-clonic seizures are typical
Moyamoya Disease - Progressive ICA stenosis; "puff of smoke" on angiography; presents in young patients
Vasculitis / PACNS - CNS vasculitis; can be isolated or part of systemic illness (e.g., Behcet's)

2. TOXIC / SUBSTANCE-RELATED

This category is highly relevant in a 20-year-old male.

Alcohol withdrawal - Most common; seizures 6-48 hours after cessation; generalized type; accounts for ~1/3 of hospital seizure admissions
Recreational drugs - Cocaine, amphetamines, MDMA, synthetic cannabinoids, bath salts
Drug intoxication - TCAs (amoxapine, clomipramine), bupropion, isoniazid, theophylline, clozapine
Benzodiazepine / barbiturate withdrawal
Carbon monoxide poisoning

3. STRUCTURAL

Traumatic Brain Injury (TBI) - Very relevant in young males; risk increases with severity; epilepsy is ~15x more common after severe TBI
Brain tumor - Seizure is the presenting sign of brain tumors in up to 50% of cases; more common with low-grade gliomas
Tuberous Sclerosis Complex - Suspect if seizures + hypopigmented ash-leaf macules; cortical tubers
Cortical dysplasia / focal cortical malformations - Common structural cause in young adults with refractory epilepsy

4. INFECTIOUS

Bacterial meningitis - Headache, photophobia, neck stiffness, fever; a 20-year-old college student is classic (meningococcal)
Viral encephalitis - HSV encephalitis: temporal lobe involvement, fever, behavioral change; herpes simplex is the most common sporadic encephalitis
Brain abscess - Focal neurologic signs; seizures arise from perilesional cortical irritation
Neurocysticercosis - Most common cause of new-onset seizure in young adults in endemic areas (Central/South America, South Asia); calcified cysts on CT
Cerebral malaria - If travel history present
HIV-related CNS disease - Toxoplasmosis, cryptococcal meningitis, HIV encephalitis itself

5. METABOLIC / SYSTEMIC

Hypoglycemia - Most common metabolic cause; typically generalized tonic-clonic; occurs in diabetics on insulin
Hyponatremia - E.g., marathon runner rehydrating with free water; MDMA use; hyponatremia is a classic cause in young patients
Hypernatremia - Diabetes insipidus setting
Hypocalcemia / hypomagnesemia - Associated with Chvostek's sign; can occur in malabsorption states
Hyperglycemia / hyperosmolar state
Hypoxia / anoxic brain injury
Hepatic encephalopathy - Liver failure with jaundice and coagulopathy
Acute porphyria - Abdominal pain + polyneuropathy + reddish-brown urine; classically precipitated by drugs or fasting
Thyrotoxicosis - Tremor, hyperreflexia, tachycardia plus seizure

NON-EPILEPTIC MIMICS (Must Exclude)

These are not seizures but are commonly misdiagnosed as such:

Mimic	Distinguishing Features
Syncope / vasovagal	Prodrome (lightheadedness, nausea), pallor, brief convulsive jerks possible
Psychogenic Non-Epileptic Seizures (PNES)	Associated with psychiatric history; movements inconsistent/waxing-waning; no postictal confusion; video-EEG is diagnostic
Migraine with aura	Visual, sensory, or motor aura; no loss of consciousness
Transient Ischemic Attack (TIA)	Focal deficits without positive motor features; no postictal period
Hypoglycemia	Confirmed by blood glucose; resolves with glucose administration
Movement disorders	Paroxysmal dyskinesias; no loss of consciousness
Sleep disorders	REM sleep behavior disorder; parasomnias

Approach Summary

In a 20-year-old male presenting with a first seizure, the highest-yield immediate considerations are:

Provoked first: rule out toxic (alcohol/drugs), infectious (meningitis), and metabolic causes
In endemic regions: neurocysticercosis is #1 until proven otherwise
Idiopathic/genetic epilepsy (especially JME) is the most common final diagnosis in this age group with normal investigations
Structural lesion (AVM, cortical dysplasia, tumor) must be excluded with MRI
EEG is key to classifying seizure type and guiding treatment

Sources: Frameworks for Internal Medicine, p. 557-568; Bradley and Daroff's Neurology in Clinical Practice; Harrison's Principles of Internal Medicine 22E

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