1. The altitude illness family

2. Presentation

• The International Classification of Headache Disorders (ICHD-3) criteria are my recollection, not from the library. They require headache within 24 h of ascent above 2500 m, usually bilateral and mild to moderate. It worsens with exertion, straining, coughing or bending, and resolves within 8 h of descent.
• The headache is typically bitemporal and throbbing, worse at night, on waking, or on standing suddenly (- Rosen's Emergency Medicine, ch. 132).
• Mechanism is multifactorial. Chemical and mechanical factors converge on the trigeminovascular system (- Harrison's 22E).

• Diagnosis needs a recent ascent to about 8000 ft or higher and headache plus at least one GI, fatigue or dizziness symptom.
• Sleep disturbance from periodic breathing is common.
• Symptoms usually clear by day 3-4. Persistent symptoms should prompt descent and a search for alternative diagnoses (- Rosen's, ch. 132).
• Lake Louise score: mild 2-4, moderate 5-9, severe 10-15 (- Tintinalli's, Table 216-2).

• Ataxia (abnormal tandem gait), confusion, drowsiness, hallucinations, then coma.
• Papilledema and retinal hemorrhages may be present.

• Early: reduced exercise tolerance and dry cough.
• Later: dyspnea at rest, pink or frothy sputum, central cyanosis, tachycardia, low-grade fever, bibasilar or right-sided crackles.
• Rosen's notes that dyspnea at rest at altitude suggests HAPE and warrants a careful chest examination.

• Rapid ascent and prior altitude illness are the strongest.
• Exertion, sleep desaturation, respiratory infection, dehydration, a low hypoxic ventilatory response, and neck irradiation or carotid body damage also raise risk.
• Poor fitness is not a risk factor (- Harrison's 22E).

3. Differential diagnosis

A. Headache, nausea and fatigue at altitude (mimics of HAH/AMS)

• Carbon monoxide poisoning. This is the most important mimic. It occurs in tents, huts and mountain-town homes with stoves, campfires or generators. Rosen's notes CO is more dangerous when combined with hypobaric hypoxia in the cold.
• Primary headaches. Migraine (with or without aura), tension-type, cluster, and primary exertional or cough headache.
• Serious intracranial causes. Subarachnoid hemorrhage, including rupture of a known aneurysm, which Harrison's says to avoid altitude for. Also cerebral venous sinus thrombosis (see below), ischemic stroke or TIA, intracranial hemorrhage, mass lesion, meningitis or encephalitis, and idiopathic intracranial hypertension.
• Metabolic and environmental. Hypoglycemia, exercise-associated hyponatremia, hypothermia, heat illness, caffeine withdrawal, and medication or alcohol effects.
• Local causes. Sinus or dental barotrauma, acute angle-closure glaucoma, and snow blindness (UV keratitis).
• Cardiac. Hypertensive crisis and acute coronary syndrome (as nausea and fatigue).

B. Ataxia or altered mental status (mimics of HACE)

1. What the syndromes are

• 37% had scoliosis.
• Levodopa response was good in 18, moderate in 6 and poor in 6.
• Nearly half had a difficult birth or a severe febrile illness in the first months of life.
• A third had difficulty walking in early childhood.
• Klawans first described it in 1981 as unilateral parkinsonism with a smaller hand or foot on the same side.

• 88% had hemiparesis first, with a mean latency of 14.7 years to dystonia. The weakness had improved markedly before the dystonia began.
• 26% had seizures.
• MRI showed basal ganglia lesions in 8 patients and cerebral hemiatrophy or diffuse atrophy in 9.
• 53% had the left side affected.
• Textbooks describe HDHA as usually the result of a static encephalopathy, a stroke, or brain injury (- Localization in Clinical Neurology 8e, Dystonia, p. 1117).

2. Clinical presentation

• Atrophy: a smaller hand, foot, limb or half of the face on the symptomatic side. Check for scoliosis.
• HPHA: unilateral bradykinesia, rigidity and rest tremor, often with a dystonic posture of the hand or foot (for example inversion).
• HDHA: a fixed or action dystonia of the arm, leg, trunk and face on one side. It is often painful and disabling.
• Other findings: mild pyramidal signs, residual hemiparesis, and seizures in some patients.
• History clues: perinatal hypoxia, a traumatic or breech delivery, early febrile illness, early hemiparesis, or a stroke.

3. Differential diagnosis

A. Unilateral parkinsonism

• Idiopathic Parkinson disease with marked asymmetry. HPHA differs in its younger onset, early dystonia, hemiatrophy, and slower, more variable progression (mean 4.2 years of follow-up in one series).
• Corticobasal syndrome: asymmetric rigidity and dystonia, apraxia, alien limb, cortical sensory loss, and no early hemiatrophy.
• Secondary structural parkinsonism: basal ganglia stroke (vascular parkinsonism), tumor, AVM or cavernoma, abscess, hematoma, and post-traumatic injury.
• Atypical parkinsonism: multiple system atrophy (MSA-P) and PSP variants (my addition).
• Young-onset and genetic causes:
  • Parkin, PINK1 and DJ-1 parkinsonism.
  • Dopa-responsive dystonia (GTP cyclohydrolase deficiency). The case-report literature notes this responds well to levodopa, unlike HPHA.
  • Wilson disease.
  • Neurodegeneration with brain iron accumulation.
  • Mitochondrial disease.
• Toxic and drug causes: manganese, carbon monoxide, MPTP, and neuroleptics or antiemetics. Drug-induced parkinsonism is usually symmetric (my addition).
• Functional parkinsonism or dystonia.

B. Hemidystonia

• Contralateral lesion of the caudate, putamen, GPe or thalamus: stroke, trauma and perinatal injury are the most common causes. Brainstem lesions (pontomesencephalic hemorrhage, diffuse axonal injury) can also cause it, and paroxysmal hemidystonia has been seen with contralateral midbrain lesions (- Localization in Clinical Neurology 8e, p. 1116-1117).
• Other secondary causes (my addition):
  • Multiple sclerosis.
  • Infection, including toxoplasmosis in HIV, TB and encephalitis.
  • CNS vasculitis and antiphospholipid syndrome.
  • Moyamoya disease.
  • Tumor.
  • Post-carotid stenting. A 2025 case report describes HDHA after a flow-diverter stent.
• Metabolic and genetic causes: Wilson disease, other inherited or metabolic dystonias, and DYT1 (which usually generalizes). The textbook lists Wilson, Lesch-Nyhan, biotin-responsive basal ganglia disease, gangliosidoses and others as symptomatic dystonias.
• Hemichorea-hemiballismus, including that from nonketotic hyperglycemia (my addition).
• Functional hemidystonia.

C. Hemiatrophy and mimics

• Dyke-Davidoff-Masson syndrome: cerebral hemiatrophy with ipsilateral skull thickening, sinus hyperpneumatization, and contralateral hemiparesis with seizures (my addition).
• Rasmussen encephalitis: progressive hemispheric atrophy with focal seizures and hemiparesis (my addition).
• Parry-Romberg syndrome (progressive facial hemiatrophy): atrophy of skin, subcutaneous tissue and bone on one side of the face, sometimes with neurologic involvement (- Bradley and Daroff's Neurology in Clinical Practice, Progressive Facial Hemiatrophy).
• Linear scleroderma (en coup de sabre).
• Hemiplegic cerebral palsy with limb growth discrepancy.
• Sturge-Weber syndrome (my addition).
• Overgrowth syndromes (hemihypertrophy, Proteus, Klippel-Trenaunay, neurofibromatosis). In these the larger side can be mistaken for the normal one (my addition).
• Peripheral causes: polio sequelae, brachial plexopathy and disuse atrophy (my addition).

4. Workup

1. History:
   • Birth and early development, early febrile illness, and trauma.
   • Hemiparesis and how well it recovered.
   • Seizures.
   • Family history.
   • Drugs and toxins.
   • Age at which atrophy was first noticed.
2. Examination:
   • Limb length and circumference.
   • Hand and foot size.
   • Face and skin.
   • Spine for scoliosis.
   • Rest tremor, rigidity and bradykinesia.
   • Dystonic postures.
   • Pyramidal signs.
   • Cortical signs such as apraxia and sensory loss.
3. Brain MRI with contrast, including SWI or T2* sequences (my addition). Look for cerebral hemiatrophy, old infarct, basal ganglia or thalamic lesions, and iron deposition. MRI is normal in a substantial minority of HPHA patients (8-67% had abnormalities across series).
4. Vascular imaging (MRA or CTA) if stroke, vasculopathy, moyamoya or a stent is in the history (my addition).
5. Labs to exclude secondary causes (my addition):
   • Ceruloplasmin, serum copper and 24-hour urine copper, with a slit-lamp exam for Kayser-Fleischer rings.
   • Glucose and HbA1c.
   • ESR, ANA and antiphospholipid antibodies.
   • HIV serology and CBC.
6. Functional imaging (supportive, not diagnostic): DaTscan or F-DOPA PET shows reduced contralateral striatal uptake in presynaptic dopaminergic disease. FDG-PET may be symmetric.
7. Genetics if onset is young or there is a family history (my addition): GCH1, parkin and other movement-disorder panels.
8. EEG if there are seizures. Serial MRI and EEG if Rasmussen encephalitis is suspected.
9. Skeletal imaging (scanogram and spine films) to document limb-length discrepancy and scoliosis.
10. Levodopa trial. It is both diagnostic, for dopa-responsive dystonia, and therapeutic.

5. Treatment

• Levodopa is the first step. Response is variable, with reports of 33-80% benefit. Dyskinesias can develop, and in one followed patient levodopa-induced dyskinesia and definite progression occurred (He 2020).
• Add-ons: dopamine agonists, amantadine, MAO-B inhibitors, and anticholinergics (for example trihexyphenidyl) if dystonia is prominent (my addition).
• Botulinum toxin for focal dystonia.
• Deep brain stimulation: only one case is reported, with subthalamic stimulation and a dramatic response despite no benefit from anticholinergics or dopamine agonists. The 2024 review suggests GPi as a reasonable target when dystonia is prominent, but this is speculative.
• Prognosis: the course is slower than typical Parkinson disease and symptoms stay unilateral longer. Progression to bilateral symptoms ranged from 0 to 53% across series.

• Botulinum toxin: 16 of 26 patients received it and responded well. It is the best-supported option.
• Oral drugs (my addition): trihexyphenidyl, baclofen, benzodiazepines, tetrabenazine, and a levodopa trial.
• Surgery: DBS (GPi) or intrathecal baclofen for severe, refractory cases (my addition). A 2026 systematic review and meta-analysis of radiofrequency lesioning (thalamotomy) for hemidystonia exists. I have only seen its title, so I can't state its results.
• Antiseizure treatment if the patient has seizures.

• Physiotherapy, occupational therapy, orthoses and shoe lifts.
• Management of scoliosis and contractures.
• Pain control.
• Counseling that the underlying injury is static, which matters most in HDHA.

6. Key takeaways

• Unilateral parkinsonism or dystonia plus a smaller ipsilateral limb or face should prompt a search for perinatal or early childhood brain injury.
• Exclude treatable and secondary causes first: Wilson disease, dopa-responsive dystonia, structural lesions, vasculopathy and autoimmune disease. Do this before labeling the case HPHA or HDHA.
• Always trial levodopa. If dystonia is troublesome, use botulinum toxin early.

1. Ranked differential for this picture

2. Diagnostic criteria

• The 2026 international consensus summarises these as: 3/3 Part A, OR 2/3 Part B, OR 2/3 Part A plus B3 (Stredny 2026).
• Part A:
  • A1 (clinical): focal seizures with or without EPC, plus unilateral cortical deficit.
  • A2 (EEG): unilateral slowing, with or without epileptiform discharges.
  • A3 (MRI): unilateral focal cortical atrophy, plus T2/FLAIR hyperintensity or atrophy or hyperintensity of the ipsilateral caudate head.
• Part B:
  • B1: EPC or progressive unilateral cortical deficit.
  • B2: progressive unilateral focal cortical atrophy on serial MRI.
  • B3: T-cell-predominant encephalitis on histopathology.
• A serial-MRI staging scheme also exists, with stage 1 showing swelling and T2 hyperintensity and stage 4 showing atrophy with normal signal (MDPI review).
• Rasmussen syndrome is a diagnosis that depends on progression. A single scan showing atrophy does not meet criteria.

• Clinical: seizures, contralateral hemiparesis, facial asymmetry, and intellectual or behavioural difficulty.
• Imaging: unilateral cerebral hemiatrophy with compensatory ipsilateral skull and sinus changes.
• A static course.
• There are two types, congenital and acquired.

• Hemidystonia with ipsilateral body or brain hemiatrophy.
• Usually preceded by hemiparesis and a perinatal injury or stroke.

3. Workup

• Birth history, early febrile illness or status, and head injury.
• When the weakness started, and whether it improved and then dystonia appeared (suggests HDHA) or it has been steadily worsening (suggests Rasmussen).
• Seizure semiology, and whether there are continuous focal jerks.
• School performance and language.
• Family history.
• Review any old imaging, because comparing scans is the quickest way to show whether the atrophy is progressive.

• Limb length and girth, hand and foot size, scoliosis, and facial asymmetry.
• Skin for port-wine stain or other neurocutaneous signs.
• Eyes, including fundus, and glaucoma screen if Sturge-Weber is suspected.
• Tone, spasticity versus dystonia, and gait.

• MRI brain with epilepsy protocol, with contrast. Add SWI and MRA/MRV.
• CT head or skull imaging for calvarial thickening and sinus changes (DDMS).
• Repeat MRI in 3-6 months if the course is unclear (my addition).
• FDG-PET shows marked hypometabolism in the affected hemisphere in Rasmussen syndrome.

• Prolonged video-EEG including sleep.
• Look for unilateral slowing, contralateral independent discharges, and EPC.
• It also separates dystonic spasms from seizures.

• Core: CBC, electrolytes, glucose, renal and liver function.
• Metabolic: lactate and ammonia.
• Wilson disease: ceruloplasmin, 24-hour urine copper, and slit-lamp exam.
• Autoimmune and inflammatory: ESR/CRP, ANA, antiphospholipid antibodies, and autoimmune encephalitis antibodies.
• Thrombophilia screen if stroke is likely.
• Infection screen where relevant.
• CSF (cells, protein, oligoclonal bands) if Rasmussen or inflammatory disease is suspected.

• Echocardiography and sickle cell screen if a stroke cause is being sought.
• Genetics (exome or a targeted panel) if the cause is unclear or onset is atypical.
• Neuropsychological assessment.
• Brain biopsy if the diagnosis of Rasmussen syndrome is uncertain and a decision hinges on it.

4. Treatment options

• Start an antiseizure medication once the seizures are confirmed as epileptic.
• Choose per local practice.
• If seizures continue despite two appropriate drugs, refer for presurgical evaluation. The Rasmussen review notes that only hemispherotomy gives definitive seizure control (Villeneuve 2022).
• Hemispherotomy is also used for refractory epilepsy in DDMS (my addition).
• It leaves permanent motor and cognitive deficits, so it is a considered decision. The affected hand and lower limb are often already poorly functional (my addition).

• Early immunotherapy: corticosteroids, IVIG and plasmapheresis. These give some benefit but don't stop the degenerative process (- Bradley and Daroff's Neurology in Clinical Practice; Villeneuve 2022).
• Newer biologics are being studied.
• Hemispherotomy is the definitive option.
• Treatment is time-sensitive, so involve a specialist epilepsy centre promptly.

• Trial of levodopa to exclude dopa-responsive dystonia.
• Trihexyphenidyl, baclofen, and benzodiazepines.
• Botulinum toxin for focal dystonia and spasticity. It helped most of the 16 HDHA patients who received it.
• If medications fail: GPi deep brain stimulation or thalamic procedures. Secondary dystonia, especially after structural brain injury, usually responds less well to DBS than primary dystonia.
• Intrathecal baclofen for severe, widespread symptoms.

• Physiotherapy, occupational therapy, orthoses, and shoe lifts.
• Orthopaedic management of contractures, scoliosis, and limb length discrepancy.

• School and learning support, psychology, and driving and safety advice.
• Sleep and mood review.
• Family counselling about the fact that a static encephalopathy won't progress, whereas Rasmussen syndrome will.

5. Practical sequence

1. Confirm the seizures with video-EEG, and look for EPC.
2. Get a skull CT and a repeat MRI with contrast to decide between static (DDMS/HDHA) and progressive (Rasmussen).
3. Do vascular imaging, a thrombophilia and inflammatory screen, Wilson testing, and a skin and eye exam.
4. Start an antiseizure medication, a levodopa trial, and botulinum toxin for dystonia.
5. Refer to an epilepsy surgery centre if seizures are refractory or the picture is progressive.