🧠 Neuroregression / Neurodegenerative Disorders - Proforma

1. Bio-Demographic Data

• Name: [Patient Name]
• Age / Sex: [Age in completed years/months] / [Male/Female]
• Informant: [Mother / Father / Primary Caregiver] — Reliability: [Good / Fair / Poor]
• Address / Residence: [Urban / Rural / Semi-urban]
• Socioeconomic Status: [Class I to V as per Modified Kuppuswamy / BG Prasad Scale (Updated 2024)]
• Date & Time of Examination: [DD/MM/YYYY, HH:MM AM/PM]

2. Chief Complaints

1. Loss of previously acquired motor / language / social milestones since `[Duration]`
2. Deterioration in school performance / memory / behavioral changes since `[Duration]`
3. Involuntary jerking movements / drop attacks / seizures since `[Duration]`
4. Progressive stiffness of limbs / difficulty walking since `[Duration]`
5. Progressive visual loss / abnormal eye movements since `[Duration]`

3. History of Present Illness (HPI)

A. Confirmation of True Neuroregression

1. Baseline Developmental Status:
   • Establish highest milestones attained in all 4 domains before onset of illness.
   • Confirm that development was normal and progressive prior to onset.
2. Distinguish from Mimics:
   • True Neuroregression: Loss of previously mastered milestones.
   • Developmental Delay: Slow rate of milestone acquisition without loss.
   • Developmental Arrest / Plateau: Cessation of new milestone acquisition without losing established skills.
   • Static Encephalopathy with Functional Decline: Growing into a deficit (e.g., worsening contractures in CP as child grows).

B. Anatomical & Systems Localization (Grey vs. White Matter vs. Basal Ganglia)

| Anatomical Compartment | Clinical Hallmarks to Elicit in History | Probable Etiologies |
|---|---|---|
| **Grey Matter (Poliodystrophy / Cortex)** | • Early intractable seizures / myoclonus<br>• Early dementia, intellectual & behavioral decline<br>• Retinal changes / macular cherry-red spot / visual loss<br>• Preserved motor function in early stages | SSPE, NCL (Batten), Tay-Sachs, Sandhoff, Alpers, Rett syndrome |
| **White Matter (Leukodystrophy)** | • Early motor loss, spasticity, hyperreflexia<br>• Early gait ataxia & pseudobulbar palsy<br>• Optic atrophy with preserved ERG<br>• Late seizures and late cognitive decline | Metachromatic Leukodystrophy (MLD), Krabbe, X-linked ALD, Canavan, Pelizaeus-Merzbacher |
| **Basal Ganglia / Extrapyramidal** | • Dystonia, choreoathetosis, rigidity, tremors<br>• Oculogyric crises, parkinsonism<br>• Preserved sensory and pyramidal tracts early | Wilson disease, Hallervorden-Spatz (PKAN), Juvenile Huntington, Glutaric aciduria Type 1 |
| **Spinocerebellar / Cerebellum** | • Prominent limb & truncal ataxia, dysmetria, nystagmus<br>• Scanning speech, titubation | Friedreich ataxia, Ataxia-Telangiectasia, Spinocerebellar ataxias |
| **Peripheral Nerves (Neuropathy)** | • Hyporeflexia / Areflexia, distal muscle wasting<br>• Hypotonia, sensory loss, foot drop | MLD, Krabbe, Charcot-Marie-Tooth, Refsum disease |

C. Chronological Domain-by-Domain Regression Mapping

| Developmental Domain | Peak Attained Milestone (Age) | Age at Onset of Loss | Current Remaining Function |
|---|---|---|---|
| **Gross Motor** | `[e.g., Running, jumping at 3y]` | `[e.g., Stumbling at 5y]` | `[e.g., Bedridden / Wheelchair]` |
| **Fine Motor** | `[e.g., Buttoning, writing at 4y]` | `[e.g., Hand clumsiness at 5y]` | `[e.g., Unable to hold cup]` |
| **Language & Speech** | `[e.g., Full fluent sentences at 3y]`| `[e.g., Vocabulary loss at 6y]` | `[e.g., Monosyllables / Mute]` |
| **Cognitive / Social** | `[e.g., Scholastic topper, cooperative]`| `[e.g., Memory loss, irritability at 6y]`| `[e.g., Does not recognize parents]` |

D. Specific Etiological Inquiry Checklist

1. Subacute Sclerosing Panencephalitis (SSPE)

• History of natural Measles infection at $<2$ years of age (or unvaccinated status).
• Stage 1: Subtle behavioral changes, emotional lability, decline in school grades, forgetfulness.
• Stage 2: Stereotyped, periodic, sudden shock-like myoclonic spasms / drop attacks / head nodding without loss of consciousness, occurring every 5–15 seconds; progressive spastic quadriparesis.
• Stage 3: Extrapyramidal rigidity, decerebrate posturing, stupor, dysphagia.
• Stage 4: Autonomic instability, akinetic mutism, flexion contractures.

2. Inborn Errors of Metabolism & Storage Disorders

• Consanguinity: High index of suspicion for autosomal recessive disorders.
• Episodic decompensation: Episodes of encephalopathy, vomiting, or ataxia precipitated by fasting, fever, or high-protein meals (MSUD, Organic acidemias, Urea cycle defects, Mitochondrial disorders).
• Abnormal odors: Mousy/musty (PKU), maple syrup (MSUD), sweaty feet (Isovaleric acidemia), cabbage-like (Tyrosinemia).
• Visual symptoms: Night blindness, tunnel vision (Refsum), loss of central vision (Tay-Sachs, NCL), Kayser-Fleischer ring/jaundice (Wilson).
• Hyperacusis / Exaggerated startle: Massive auditory startle response to sudden sound (Tay-Sachs disease).
• Organomegaly: Abdominal distension due to hepatosplenomegaly (Niemann-Pick Type A/C, Gaucher Type 2/3, GM1 gangliosidosis, Mucopolysaccharidoses; absent in Tay-Sachs).

4. Birth, Immunization & Dietary History

A. Birth History

• Antenatal infections (TORCH, HIV).
• Natal: Birth weight, gestational age, birth asphyxia (important to differentiate static perinatal injury from progressive neurodegeneration).

B. Immunization History

• NIS compliance; Measles / MMR vaccination status (Number of doses, age at administration, occurrence of breakthrough measles infection).

C. Dietary History & 24-Hour Recall

• Protein intake calculation; aversion to high-protein foods (urea cycle disorders); daily calorie and protein deficits.

| Meal Time | Food Item & Composition | Quantity | Energy (kcal) | Protein (g) |
|---|---|---|---|---|
| Breakfast | `[Items]` | `[Amount]` | `[kcal]` | `[g]` |
| Lunch | `[Items]` | `[Amount]` | `[kcal]` | `[g]` |
| Snacks | `[Items]` | `[Amount]` | `[kcal]` | `[g]` |
| Dinner | `[Items]` | `[Amount]` | `[kcal]` | `[g]` |
| **Total** | | | **`[Total kcal]`** | **`[Total Protein g]`** |
| **Recommended (RDA)** | | | **`[RDA kcal]`** | **`[RDA Protein g]`** |
| **Deficit / Excess** | | | **`[Deficit kcal]`** | **`[Deficit g]`** |

5. Physical Examination

A. General Physical Examination

• Vitals: Heart rate, Respiratory rate, Blood pressure ($Z$-score / centile), Temperature.
• Anthropometry: Weight, Height, Head Circumference ($Z$-score: Macrocephaly in Alexander, Canavan, Tay-Sachs after 1y, GM2; Microcephaly in Rett, NCL, Alpers).
• General Markers: Pallor, Icterus, Hepatosplenomegaly, Coarse facial features, Gingival hypertrophy, Skeletal dysostosis multiplex.
• Neurocutaneous & Skin Markers:
  • Telangiectasias (Ataxia-Telangiectasia)
  • Angiokeratomas (Fabry disease, Fucosidosis)
  • Ichthyosis (Refsum, Sjogren-Larsson)
  • Kinky / brittle hair (Menkes disease)
  • Pigmentary changes (X-linked ALD - bronzing of skin / adrenal insufficiency)

6. Central Nervous System (CNS) Examination

A. Higher Mental Functions (HMF)

• Sensorium: [Conscious / Encephalopathic / Stuporous / Vegetative state]
• Attention & Cognition: [Mini-Mental / Age-appropriate score; ability to follow commands]
• Speech: [Intact / Dysarthric / Aphasic / Echolalia / Stereotypic vocalizations / Mute]
• Behavioral Abnormalities: [Hyperactivity, aggression, emotional lability, dementia]

B. Cranial Nerves & Ophthalmological Survey

• CN II (Optic):
  • Visual tracking & fixation: [Intact / Impaired / Cortical blindness]
  • Pupillary reflexes: [Brisk / Sluggish / Paradoxical]
  • Fundoscopy:
    • Macula: [Normal / Cherry-red spot (Tay-Sachs, Niemann-Pick, Sandhoff) / Bull's eye maculopathy (NCL)]
    • Optic Disc: [Normal / Primary Optic Atrophy (MLD, Krabbe, ALD) / Papilledema]
    • Retina: [Retinitis pigmentosa (NCL, Mitochondrial, Refsum)]
• Extraocular Movements (CN III, IV, VI):
  • Saccades & Pursuits: [Smooth / Oculomotor apraxia (Ataxia-Telangiectasia, Gaucher Type 3) / Supranuclear vertical gaze palsy (Niemann-Pick Type C)]
• Lower Cranial Nerves (CN IX, X, XII):
  • Bulbar / Pseudobulbar palsy: [Swallowing difficulty, exaggerated jaw jerk, pooling of secretions, spastic tongue].

C. Motor System & Involuntary Movements

• Involuntary Movements:
  • Myoclonus / Periodic Spasms: [Present / Absent: Stereotyped, synchronous, recurring every __ seconds, precipitating drop attacks without loss of consciousness]
  • Chorea / Dystonia / Athetosis: [Present / Absent]
• Muscle Bulk: [Normal / Generalized wasting / Distal neurogenic atrophy].
• Muscle Tone:
  • Upper & Lower Limbs: [Spasticity (Clasp-knife) / Lead-pipe or Cogwheel rigidity / Hypotonia / Dystonic posturing / Decerebrate vs Decorticate rigidity].
  • Modified Ashworth Scale (MAS): [Grade 0 to 4].
• Power (MRC Scale): [Grade 0 to 5 in all four limbs].
• Reflexes:
  • Deep Tendon Reflexes: [Brisk (3+/4+) with clonus / Depressed (MLD, Krabbe neuropathy)].
  • Plantar Response: [Bilateral extensor / Flexor].
  • Primitive Reflexes: [Grasp, Palmomental, Snout reflex present (Frontal release)].

7. Other Systemic Examination

• Cardiovascular System: Murmurs, cardiomyopathy (Friedreich, Mitochondrial, Pompe).
• Abdomen:
  • Liver: [Size in cm below right costal margin, span, consistency, surface]
  • Spleen: [Size in cm below left costal margin, consistency (massive in Gaucher, Niemann-Pick)]
• Respiratory System: Aspiration signs, respiratory pattern.

8. Clinical Summary & Spoken Diagnosis