Doose Syndrome, GEFS+ & Rasmussen Encephalitis
This topic addresses three distinct but important childhood epilepsy syndromes that occupy unique positions in the ILAE classification framework. Epilepsy with myoclonic-atonic seizures (formerly Doose syndrome) is a developmental and epileptic encephalopathy of early childhood characterized by the hallmark myoclonic-atonic (drop attack) seizure. Genetic epilepsy with febrile seizures plus (GEFS+) is a familial syndrome with a wide phenotypic spectrum ranging from simple febrile seizures to severe epileptic encephalopathies, including Dravet syndrome, within the same family. Rasmussen encephalitis is a chronic, progressive, unilateral inflammatory brain disorder that causes intractable focal seizures, epilepsia partialis continua (EPC), and progressive hemispheric atrophy. Understanding these syndromes is essential for accurate diagnosis, appropriate treatment selection (including avoidance of medications that worsen certain seizure types), genetic counseling, and surgical decision-making.
Bottom Line
- Doose syndrome (epilepsy with myoclonic-atonic seizures): Onset age 2–6 years in a previously normally developing child; hallmark seizure is the myoclonic-atonic drop attack; generalized spike-wave and polyspike-wave on EEG; ketogenic diet is highly effective (often first-line); AVOID carbamazepine and phenytoin; two-thirds achieve remission but one-third develop refractory epilepsy with cognitive decline
- GEFS+ (genetic epilepsy with febrile seizures plus): Familial syndrome with wide intrafamilial phenotypic variability; SCN1A, SCN1B, SCN2A, GABRG2 mutations; spectrum from benign febrile seizures → FS+ (persisting beyond age 6) → Dravet syndrome; most family members have a benign course; critical concept for genetic counseling
- Rasmussen encephalitis: Chronic progressive unilateral hemispheric inflammation; onset typically age 2–10 years; focal motor seizures, epilepsia partialis continua, progressive hemiparesis and cognitive decline; T-cell-mediated pathology with progressive hemispheric atrophy on MRI; immunotherapy is temporizing only; functional hemispherectomy is the only definitive treatment, stopping seizures in 70–80%
- EPC: Epilepsia partialis continua is not exclusive to Rasmussen encephalitis; also seen in stroke, cortical dysplasia, tumors, mitochondrial disorders (MELAS), and autoimmune encephalitis
Epilepsy With Myoclonic-Atonic Seizures (Doose Syndrome)
Definition and Classification
Epilepsy with myoclonic-atonic seizures (EMAtS), previously known as Doose syndrome or myoclonic-astatic epilepsy (MAE), is classified by the ILAE 2022 as a childhood-onset developmental and epileptic encephalopathy. The syndrome was first described by Hermann Doose in 1970 and is characterized by the onset of multiple generalized seizure types—always including the hallmark myoclonic-atonic seizure—in a previously normally developing child between ages 2 and 6 years.
Epidemiology
- Accounts for approximately 1–2% of childhood-onset epilepsies
- Age of onset: 2–6 years (peak 3–4 years); onset before age 2 is atypical and should prompt consideration of alternative diagnoses
- Male-to-female ratio approximately 2:1
- Previously normal development is a key diagnostic criterion; children with preexisting developmental delay more likely have Lennox-Gastaut syndrome
Genetics
EMAtS has complex and polygenic inheritance, with a strong genetic predisposition evidenced by high rates of family history of febrile seizures and epilepsy (approximately 30–50% of families). Single-gene causes are identified in a minority of patients:
| Gene | Protein/Channel | Mechanism | Clinical Notes |
|---|---|---|---|
| SLC2A1 | GLUT1 glucose transporter | Impaired glucose transport across the blood-brain barrier | GLUT1 deficiency; particularly responsive to ketogenic diet (first-line therapy); consider in any EMAtS patient |
| SCN1A | NaV1.1 sodium channel | Haploinsufficiency of inhibitory interneuron sodium channels | Overlaps with Dravet and GEFS+ spectrum; avoid sodium channel blockers |
| CHD2 | Chromodomain helicase DNA-binding protein 2 | Chromatin remodeling; affects gene expression | Photosensitivity common; intellectual disability variable |
| SLC6A1 | GAT-1 GABA transporter | Impaired GABA reuptake at synapses | Myoclonic-atonic seizures with learning difficulties |
| SYNGAP1 | Synaptic Ras GTPase-activating protein 1 | Disrupted synaptic plasticity and NMDA receptor signaling | Intellectual disability is typically prominent |
| STX1B | Syntaxin-1B (SNARE complex) | Impaired synaptic vesicle fusion and neurotransmitter release | Also associated with fever-sensitive seizures |
Clinical Features
The onset is often explosive, with frequent seizures of multiple generalized types appearing over days to weeks. Febrile seizures may precede the onset of EMAtS in up to 30% of patients.
| Seizure Type | Frequency | Description |
|---|---|---|
| Myoclonic-atonic (hallmark) | 100% (required) | Brief myoclonic jerk (upward) immediately followed by atonic drop; the child falls suddenly—"head nod" in mild forms, full-body drop in severe forms; very brief (<1–2 seconds); may cause facial/head injuries; dozens to hundreds per day |
| Myoclonic | ~85% | Brief bilateral myoclonic jerks without subsequent atonic component; may involve upper limbs preferentially |
| Generalized tonic-clonic | ~70% | Often the presenting seizure type; may precede myoclonic-atonic seizures by weeks to months |
| Atypical absence | ~60% | Subtle behavioral arrest with eyelid fluttering; may be prolonged; can evolve to absence status epilepticus |
| Nonconvulsive status epilepticus | ~40% | Prolonged obtundation with continuous or near-continuous myoclonic jerks and subtle absences; can last hours to days; may be misdiagnosed as encephalopathy |
| Tonic seizures | Atypical; raises concern for LGS | Pure tonic seizures are NOT characteristic of EMAtS; their presence should prompt reconsideration of the diagnosis toward Lennox-Gastaut syndrome |
EEG Features
- Interictal: Generalized 2–6 Hz spike-and-wave and polyspike-and-wave complexes; background may show prominent 4–7 Hz theta rhythms (a characteristic feature described by Doose); background is initially normal but may deteriorate with refractory disease
- Ictal (myoclonic-atonic seizure): Brief generalized polyspike discharge (myoclonic component) immediately followed by high-amplitude slow wave with electrodecrement (atonic component)
- Key distinction from LGS: No generalized paroxysmal fast activity (GPFA) during sleep; no slow (<2.5 Hz) spike-and-wave pattern; background theta rhythms rather than persistent diffuse slowing
Treatment
| Therapy | Role | Evidence/Notes |
|---|---|---|
| Ketogenic diet | Often first-line; highly effective | 50–80% of patients achieve ≥50% seizure reduction; some achieve seizure freedom; particularly effective if SLC2A1 (GLUT1 deficiency) is present; should be considered early in the disease course |
| Valproate | First-line pharmacotherapy | Broad-spectrum; effective against myoclonic, absence, and GTC seizures; weight gain, tremor, hepatotoxicity risk in young children; check POLG before use in children <2 years |
| Ethosuximide | Adjunctive (especially for absences) | Effective against absence and myoclonic-atonic seizures when combined with valproate; may worsen GTC seizures if used alone |
| Clobazam | Adjunctive; broad spectrum | Useful add-on for multiple seizure types; tolerance may develop; sedation |
| Levetiracetam | Adjunctive | Modest efficacy; generally safe; behavioral side effects may limit use |
| Corticosteroids/ACTH | Rescue therapy for nonconvulsive SE | May be helpful for refractory seizures and nonconvulsive status epilepticus; short-term use |
Medications to AVOID in Doose Syndrome
- Carbamazepine (Tegretol): Worsens myoclonic and absence seizures; can precipitate myoclonic status epilepticus
- Oxcarbazepine (Trileptal): Same mechanism as carbamazepine; equally harmful
- Phenytoin (Dilantin): Worsens generalized seizures, particularly myoclonic and absence types
- Vigabatrin: May worsen myoclonic seizures
- Rationale: Sodium channel blockers preferentially suppress tonic-clonic seizures but can paradoxically exacerbate myoclonic, atonic, and absence seizures in generalized epilepsy syndromes
Prognosis
- Favorable outcome (~60–70%): Seizures remit within 1–3 years of onset; cognitive outcome is normal or near-normal; children with early seizure control and normal background EEG have the best prognosis
- Unfavorable outcome (~30–40%): Refractory seizures, particularly nonconvulsive status epilepticus; progressive cognitive decline; may evolve toward a Lennox-Gastaut-like phenotype with tonic seizures and slow spike-wave
- Predictors of poor outcome: early onset of nonconvulsive status epilepticus, persistent EEG background abnormalities, tonic seizures, and failure to respond to initial treatment
Doose Syndrome vs. Lennox-Gastaut Syndrome
| Feature | Doose Syndrome (EMAtS) | Lennox-Gastaut Syndrome (LGS) |
|---|---|---|
| Prior development | Normal development; no prior neurological disorder | Often preceded by West syndrome or structural brain lesion; developmental delay frequently present at onset |
| Hallmark seizure | Myoclonic-atonic (drop attacks) | Tonic seizures (especially during sleep) |
| Tonic seizures in sleep | Absent (critical distinguishing feature) | Present (mandatory diagnostic criterion for LGS) |
| Interictal EEG | 2–6 Hz generalized spike-wave; theta rhythms; NO paroxysmal fast activity | Slow (<2.5 Hz) spike-wave; paroxysmal fast activity (10–20 Hz) during NREM sleep |
| Neuroimaging | Normal | Often abnormal (cortical dysplasia, hypoxic-ischemic encephalopathy, tuberous sclerosis) |
| Response to ketogenic diet | Excellent (50–80% respond) | Modest (40–50% respond) |
| Prognosis | ~60–70% seizure freedom; normal IQ in responders | Drug-resistant in >90%; progressive cognitive decline |
Genetic Epilepsy With Febrile Seizures Plus (GEFS+)
Definition and Concept
GEFS+ is a familial epilepsy syndrome characterized by a wide phenotypic spectrum of seizure disorders occurring within the same family. First described by Scheffer and Berkovic in 1997, GEFS+ is defined at the family level rather than the individual level—it requires at least two family members with seizure disorders within the GEFS+ spectrum. The concept is clinically important because it demonstrates how a single genetic variant can produce vastly different epilepsy phenotypes even among closely related individuals.
Genetics
| Gene | Protein/Channel | Inheritance | Phenotypic Spectrum |
|---|---|---|---|
| SCN1A | NaV1.1 sodium channel α-subunit | Autosomal dominant (variable penetrance) | Most common cause; missense variants more commonly cause GEFS+ (vs. truncating variants causing Dravet); same variant can cause FS in one family member and Dravet in another |
| SCN1B | NaV β1-subunit | Autosomal dominant | First gene identified in GEFS+ families; modulates sodium channel gating |
| SCN2A | NaV1.2 sodium channel α-subunit | Autosomal dominant | Febrile seizures and neonatal seizures; gain-of-function variants may respond to sodium channel blockers |
| GABRG2 | GABAA receptor γ2-subunit | Autosomal dominant | Impaired GABAergic inhibition; associated with typical febrile seizures, childhood absence epilepsy, and GEFS+ phenotype |
| GABRD | GABAA receptor δ-subunit | Autosomal dominant | Less common; contributes to tonic inhibition |
| STX1B | Syntaxin-1B (presynaptic) | Autosomal dominant | Temperature-sensitive seizures; overlaps with EMAtS genetics |
Clinical Spectrum
GEFS+ encompasses a range of phenotypes within a single family, from the mildest (simple febrile seizures) to the most severe (Dravet syndrome). The phenotype of any individual family member is influenced by additional genetic modifiers and environmental factors.
| Phenotype | Severity | Clinical Features | Prognosis |
|---|---|---|---|
| Simple febrile seizures | Mildest | Typical febrile seizures resolving by age 6; brief, generalized; triggered by fever | Excellent; self-limited |
| Febrile seizures plus (FS+) | Mild | Febrile seizures persisting beyond age 6 or occurring with afebrile generalized tonic-clonic seizures; onset may be before 6 months (atypical age) | Generally favorable; most achieve seizure freedom with treatment |
| FS+ with absence seizures | Mild–moderate | FS+ phenotype plus typical absence seizures; may resemble childhood absence epilepsy | Good; usually responsive to valproate or ethosuximide |
| FS+ with myoclonic seizures | Moderate | FS+ phenotype plus myoclonic seizures; may resemble juvenile myoclonic epilepsy | Variable; generally controllable |
| FS+ with atonic seizures | Moderate | FS+ phenotype plus myoclonic-atonic seizures; overlaps with Doose syndrome | Variable |
| FS+ with temporal lobe epilepsy | Moderate | FS+ phenotype followed by focal temporal lobe epilepsy; may develop hippocampal sclerosis | Variable; may become drug-resistant |
| Dravet syndrome | Severest | Prolonged febrile seizures in infancy → multiple seizure types → intellectual disability → drug-resistant epilepsy | Poor; lifelong drug-resistant epilepsy; cognitive impairment; SUDEP risk |
GEFS+ and Genetic Counseling
- GEFS+ is defined at the family level: the key diagnostic criterion is at least two family members with seizure phenotypes fitting the GEFS+ spectrum
- A parent with "benign" febrile seizures who carries an SCN1A missense variant can have a child with Dravet syndrome (de novo loss-of-function variant in the same gene, or the same variant with different expressivity)
- Penetrance is incomplete: not all carriers of a GEFS+ variant will develop seizures
- Genetic testing identifies a causative variant in approximately 20–30% of GEFS+ families; a negative test does not exclude the diagnosis
- Recurrence risk counseling must account for variable expressivity—predicting the severity of epilepsy in an at-risk child is not possible based on the family variant alone
- The GEFS+ concept illustrates why family history is essential: asking about febrile seizures in parents, siblings, and extended relatives can reveal the familial pattern
Treatment Considerations in GEFS+
- Most individuals with FS+ have a benign course and may not require long-term antiseizure medication
- Standard treatment for the specific seizure/epilepsy phenotype applies (e.g., valproate for generalized epilepsy, ethosuximide for absence seizures)
- If an SCN1A variant is identified, sodium channel blockers should be used with caution—they are well-tolerated in many FS+ patients but can worsen seizures in patients trending toward the Dravet end of the spectrum
- Any child in a GEFS+ family with worsening seizures on sodium channel blockers should be urgently evaluated for Dravet syndrome
Rasmussen Encephalitis
Definition and Classification
Rasmussen encephalitis (RE) is a rare, chronic, progressive, inflammatory disorder affecting one cerebral hemisphere, leading to intractable focal seizures, progressive hemiparesis, cognitive decline, and hemispheric atrophy. It was first described by Theodore Rasmussen in 1958. The ILAE 2022 classification lists it as an epilepsy syndrome with variable age of onset that is associated with developmental and epileptic encephalopathy or progressive neurologic deterioration.
Epidemiology
- Rare: estimated incidence of 1–2 per 10 million per year
- Typical onset: 2–10 years (median ~6 years); adult-onset cases account for approximately 10% and tend to have a slower course
- No sex predilection; no ethnic or geographic predisposition
- Almost always unilateral; bilateral involvement is exceptionally rare and should prompt consideration of alternative diagnoses
Pathophysiology
Rasmussen encephalitis is a T-cell-mediated autoimmune process targeting neurons in one hemisphere:
- Pathology: CD8+ cytotoxic T-lymphocyte infiltration; microglial nodules; astrogliosis; neuronal loss; progressive cortical and subcortical atrophy confined to one hemisphere
- Anti-GluR3 antibodies: Antibodies against the GluR3 (GRIA3) subunit of the AMPA-type glutamate receptor were initially proposed as pathogenic but are now considered a secondary phenomenon; they are not present in all patients and can be found in other epilepsies
- T-cell clonal expansion: Clonally expanded CD8+ T cells within the affected hemisphere, with granzyme B-mediated apoptosis of neurons—this is the primary effector mechanism
- Possible triggers: An initial viral infection or other immune trigger is hypothesized but not proven; no consistent viral agent has been identified
Clinical Features and Stages
| Stage | Duration | Clinical Features | MRI Findings |
|---|---|---|---|
| Prodromal | Months to years | Infrequent focal seizures (often motor); relatively normal interictal examination; seizures may initially respond to ASMs; mild hemiparesis may develop | Subtle T2/FLAIR signal changes in the affected hemisphere; may appear normal initially |
| Acute/active | 4–8 months (median) | Rapidly increasing seizure frequency; epilepsia partialis continua develops in ~50–80%; progressive hemiparesis (contralateral to affected hemisphere); hemianopia; cognitive decline; aphasia (if dominant hemisphere involved) | Progressive unilateral cortical and subcortical atrophy; T2/FLAIR signal abnormalities; caudate head atrophy (early sign); enlargement of ipsilateral ventricle |
| Residual/burnout | Indefinite | Seizures may decrease in frequency but rarely stop; fixed hemiplegia; hemianopia; cognitive impairment; the inflammatory process may "burn out" but neurologic deficits persist | Severe unilateral hemispheric atrophy; ex vacuo ventricular enlargement; volume loss predominantly in the insular cortex, perisylvian region, and caudate |
Diagnostic Criteria
The European Consensus Criteria (Bien et al., 2005) define RE based on clinical, EEG, and MRI features:
| Criterion | Part A (all 3 required) | Part B (any 2 of 3 required) |
|---|---|---|
| Clinical | Focal seizures (with or without EPC) and unilateral cortical deficit(s) | EPC or progressive unilateral cortical deficit(s) |
| EEG | Unihemispheric slowing ± epileptiform activity and unilateral seizure onset | Unihemispheric slowing ± epileptiform activity and unilateral seizure onset |
| MRI | Unihemispheric focal cortical atrophy and at least one of: grey or white matter T2/FLAIR hyperintensity, or atrophy of ipsilateral caudate head | Progressive unihemispheric focal cortical atrophy |
| Histopathology | Not required if Part A criteria met | T-cell-dominated encephalitis with activated microglial cells (typically forming nodules) and reactive astrogliosis |
Treatment
| Therapy | Role | Efficacy/Notes |
|---|---|---|
| Antiseizure medications | Symptomatic; early and residual phase | May partially control seizures early but become increasingly ineffective as the disease progresses; multiple ASMs typically required; no specific ASM is preferred |
| Corticosteroids (IV methylprednisolone, oral prednisone) | First-line immunotherapy | May transiently reduce seizure frequency and slow progression; chronic steroids carry significant side effects; often used as a bridge to surgery |
| Intravenous immunoglobulin (IVIg) | Immunomodulatory | Periodic infusions may stabilize the disease temporarily; better evidence in adult-onset RE; does not halt disease progression |
| Tacrolimus | T-cell-targeted immunosuppression | Calcineurin inhibitor targeting T-cell activation; some case series report slowing of progression; nephrotoxicity, infection risk |
| Rituximab | Anti-CD20 B-cell depletion | Reports of benefit in some patients; addresses B-cell-mediated but not the primary T-cell-mediated component; limited evidence |
| Functional hemispherectomy | Definitive treatment | Seizure freedom in 70–80% of patients; stops disease progression; results in contralateral hemiplegia, hemianopia, and (if dominant hemisphere) aphasia; earlier surgery associated with better functional outcomes due to neuroplasticity |
Timing of Hemispherectomy in Rasmussen Encephalitis
- The decision to proceed with hemispherectomy is one of the most challenging in epilepsy surgery because it involves accepting certain neurologic deficits (hemiplegia, hemianopia) to achieve seizure control and halt cognitive decline
- Arguments for earlier surgery: The disease will inevitably cause progressive hemiparesis and cognitive decline; younger children have greater neuroplasticity and can compensate for language and motor loss more effectively; delaying surgery does not preserve neurologic function—it allows further irreversible damage
- Arguments for delaying surgery: If the dominant hemisphere is involved, language functions may partially lateralize to the contralateral hemisphere before surgery; immunotherapy may provide a window of stabilization
- Practical approach: Most centers recommend hemispherectomy when seizures are refractory to medical therapy and progressive neurologic decline is documented; immunotherapy can serve as a bridge, particularly if the dominant hemisphere is affected
- Postoperative outcomes: seizure freedom in 70–80%; contralateral hemiplegia (expected); hand function is lost but proximal arm function is partially preserved; hemianopia (expected); language recovery is excellent if surgery is performed before age 6 in dominant hemisphere
Red Flags: When to Suspect Rasmussen Encephalitis
- Any child with progressively intractable focal seizures, especially if seizures originate from one hemisphere only
- Development of epilepsia partialis continua (continuous focal clonic jerking) in a child
- Progressive unilateral neurological deficits (hemiparesis, hemianopia, aphasia) with ongoing seizures
- Unilateral hemispheric atrophy on serial MRI, particularly involving the insular cortex and caudate head
- Do NOT wait for the full clinical picture before referring to an epilepsy surgery center—earlier evaluation enables earlier intervention and better cognitive outcomes
Epilepsia Partialis Continua (EPC)
Epilepsia partialis continua (EPC) is a specific form of focal motor status epilepticus characterized by continuous or near-continuous focal clonic jerking of a body part, typically a hand, arm, or face, lasting hours to days to even years. While EPC is a hallmark of Rasmussen encephalitis, it occurs in many other neurologic conditions.
Etiologies of EPC
| Etiology | Clinical Context | Key Features |
|---|---|---|
| Rasmussen encephalitis | Children (2–10 years) | Progressive unilateral disease with hemispheric atrophy; EPC in 50–80% of patients |
| Cortical dysplasia | Any age; congenital | Non-progressive; focal MRI lesion; may be surgically resectable |
| Acute/subacute stroke | Adults (mainly); children with perinatal stroke | Cortical involvement required; may appear days to weeks after the ischemic event |
| MELAS (mitochondrial encephalopathy) | Young adults; maternal inheritance | Strokelike episodes with EPC; elevated lactate; m.3243A>G mutation most common; seizures may involve posterior cortex |
| Brain tumors | Any age | Low-grade gliomas, DNET, gangliogliomas; EPC may be the presenting symptom |
| Autoimmune encephalitis | Any age | Anti-NMDA, anti-LGI1, anti-CASPR2 antibodies; EPC may respond to immunotherapy |
| Nonketotic hyperglycemia | Elderly diabetic patients | Focal motor seizures/EPC with contralateral cortical T2 signal changes; reversible with glucose correction |
| Infections (encephalitis, abscess) | Any age | Viral encephalitis (HSV, tick-borne); brain abscess with cortical irritation |
Key Points About EPC
- EPC is often highly resistant to antiseizure medications; aggressive polytherapy may reduce but rarely eliminates the jerking
- EPC can occur with preserved consciousness—patients may be awake and alert while one hand jerks continuously
- In EPC, scalp EEG may NOT show clear ictal correlates because the cortical generator may be too small or deep for scalp recording; a "normal" EEG does not rule out EPC
- Treatment should target the underlying etiology (e.g., immunotherapy for Rasmussen, glucose correction for hyperglycemia, tumor resection, mitochondrial-specific therapy for MELAS)
- Surgical resection of the epileptogenic cortex is the most effective treatment when a focal structural lesion is identified and is amenable to resection
Comparison of Doose Syndrome, GEFS+, and Rasmussen Encephalitis
| Feature | Doose Syndrome (EMAtS) | GEFS+ | Rasmussen Encephalitis |
|---|---|---|---|
| ILAE category | DEE (childhood onset) | Self-limited familial (neonatal/infantile onset) | DEE / progressive deterioration (variable age) |
| Age of onset | 2–6 years | 6 months – childhood (variable) | 2–10 years (typical); adults ~10% |
| Sex predominance | Male (2:1) | None | None |
| Etiology | Genetic (polygenic; SLC2A1, SCN1A, CHD2, SLC6A1) | Genetic (monogenic AD; SCN1A, SCN1B, GABRG2) | Immune (T-cell mediated; ± anti-GluR3 Ab) |
| Laterality | Bilateral/generalized | Bilateral/generalized | Unilateral (always) |
| Hallmark seizure | Myoclonic-atonic (drop attack) | Febrile seizures persisting beyond age 6 | Focal motor seizures; epilepsia partialis continua |
| Other seizure types | GTC, absence, myoclonic, NCSE | GTC, absence, myoclonic, focal (varies by phenotype) | Secondary GTC; rarely other focal types |
| EEG | Generalized SW 2–6 Hz; polyspike-wave; theta rhythms | Variable; may be normal or show generalized SW | Unilateral slowing; focal discharges; multifocal within one hemisphere |
| MRI | Normal | Normal (unless hippocampal sclerosis develops) | Progressive unilateral hemispheric atrophy |
| Treatment | Ketogenic diet, VPA, ETX, CLB | Standard ASMs for seizure type | Immunotherapy (temporizing); hemispherectomy (definitive) |
| Medications to avoid | CBZ, OXC, PHT (worsen myoclonic/absence) | Na+ channel blockers if trending toward Dravet | None specifically contraindicated |
| Family history | 30–50% have FS/epilepsy | Positive by definition (≥2 affected members) | No familial predisposition |
| Prognosis | ~60–70% remit; ~30–40% refractory + cognitive decline | Most benign; Dravet end is severe | Progressive if untreated; seizure-free in 70–80% post-hemispherectomy |
Diagnostic Approach
When to Consider Each Diagnosis
- Think Doose syndrome when: A previously normally developing child aged 2–6 presents with explosive onset of multiple generalized seizure types, particularly frequent myoclonic-atonic drop attacks; EEG shows generalized spike-wave with prominent theta rhythms; no tonic seizures (which favor LGS); normal MRI
- Think GEFS+ when: A child with febrile seizures has a family history of multiple relatives with febrile seizures or epilepsy; febrile seizures persist beyond age 6; afebrile seizures develop; different family members have different epilepsy phenotypes
- Think Rasmussen encephalitis when: A child develops focal motor seizures or EPC that progressively worsen; neurologic examination shows progressive unilateral deficits; MRI demonstrates progressive unilateral hemispheric atrophy; seizures are refractory to multiple ASMs
- Key red flags for misdiagnosis: Tonic seizures in a child diagnosed with Doose syndrome (reconsider LGS); bilateral hemispheric involvement in suspected Rasmussen (reconsider autoimmune encephalitis or bilateral cortical dysplasia); attributing Dravet syndrome to a child in a GEFS+ family when the phenotype is mild (overdiagnosis can lead to unnecessary treatment restrictions)
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