Protocol - Disease Progression and Regression - 0-24 Months

The Newcastle Paediatric Mitochondrial Disease Scale (NPMDS)

0 - 24 months

Date of assessment:

Age at assessment:

Parental consanguinity:

Age at presentation:

Age at clinical diagnosis:

Clinical diagnosis:

Genotype if known:

Biochemical phenotype if known:

Basis of clinical diagnosis e.g. MRI, blood / CSF lactate

Information regarding pregnancy

• reduced fetal movements _____Y___ N___ unknown_____

• cardiomyopathy on antenatal scans ___ Y___ N___ unknown________

• abnormalities on fetal anomaly scan ___ Y___ N___unknown________ Please specify_______________________________________________

• other:

Neonatal information:

• gestational age _______weeks

• delivery method (NVD vs instrumental vs C/S) _______

• birth weight _______kg

• resuscitation and ventilation ___ Y___ N___unknown__ _______

Please specify_______________________________________________

Scores: Sections I-III:

Section IV:

Section I: Current Function

Rate function during the preceding 2 week period only according to caregiver

interview. Indicate the score that best fits patient’s functional status independently of the nature of the signs.

1. Vision

0. Normal. No parental concerns
1. Mild. Limited eye or head movement to large objects or parental face in visual field
2. Moderate. No response to large objects or parental face in the visual field
3. Severe. No response to light

2. Hearing

0. Normal
1. Mild. Body, head or eye movement only to loud noise
2. Moderate. No reaction to loud noise
3. Severe. No hearing (even with aid)

3. Communication (assessed with appropriate regard for age)

0. Normal. Age appropriate communication
1. Mild. Delayed development of communication
2. Moderate. Communication unintelligible to parents or completely reliant on non-verbal communication
3. Severe. Not communicating effectively in any form

4. Feeding

0. Normal
1. Mild. Difficulties in sucking / coughing / anorexia / wheezy with feeds or occasional choking
2. Moderate. Supplementary enteral feeding or recurrent aspiration pneumonia
3. Severe. Exclusive enteral feeding (gastrostomy / NG tube). Nil by mouth

5. Mobility

0. Normal. No concerns. Age appropriate mobility
1. Mild. Clumsy age appropriate mode of mobility
2. Moderate. Mobile but through age inappropriate mode
3. Severe. Immobile

Section II: System Specific Involvement

Rate system specific involvement during the preceding 6 month period only (or since birth if the child is less than 6 months old) unless otherwise stated in the question. Scores should be assigned according to caregiver interview, clinician’s knowledge of the patient and clinical notes.

1. Seizures

0. None
1. Mild. Myoclonic or absence seizures only or < 1 generalised tonic-clonic seizure/month
2. Moderate. > 5 generalized tonic-clonic seizures/month or > 20 absence or myoclonic seizures/month
3. Severe. Status epilepticus or intractable seizures

2. Encephalopathy

0. None
1. Mild. Abnormal sleepiness / lethargy. Waking only for feeds
2. Moderate. Recurrent episodes of mild encephalopathy (> 2/year)
3. Severe. Life threatening encephalopathy - requires artificial ventilation

3. Gastrointestinal

0. Normal.
1. Mild. Constipation or unexplained vomiting / diarrhoea > 3/week
2. Moderate. Severe constipation (no relief with laxative treatment) or unexplained vomiting / diarrhoea every day or surgical intervention for dysmotility
3. Severe Malabsorption / Failure to thrive

4. Endocrine

0. Normal.
1. Mild. Biochemical evidence of impaired function
2. Moderate. Endocrine failure requiring replacement therapy
3. Severe. Endocrine decompensation (e.g. diabetic ketoacidosis, Addisonian crisis)

5. Respiratory

0. Normal
1. Mild. Abnormal respiratory pattern not requiring therapy / hospitalization
2. Moderate. Abnormal respiration requiring oxygen flow or hospitalisation but not ventilation
3. Severe. Abnormal respiration requiring artificial ventilation

6. Cardiovascular- over preceding 12 months

0. Normal
1. Mild. Asymptomatic ECG change
2. Moderate. Abnormal echocardiogram (e.g. cardiomegaly) or sustained / symptomatic arrhythmia on ECG
3. Severe. Decompensated cardiomyopathy or requiring pacing device / defibrillator / ablation

7. Renal

0. Normal
1. Mild. Impaired function but no change in diet or therapy required
2. Moderate. Impaired function requiring restricted protein diet
3. Severe. Failure requiring transplant / dialysis

8. Liver

0. Normal
1. Mild. Mildly impaired Liver Function Tests (LFTs). Normal albumin and coagulation. No symptoms of hepatic failure
2. Moderate. Impaired LFTs with symptoms (e.g. jaundice, coagulation anomalies, oedema)
3. Severe. Failure requiring hospitalisation and / or transplantation

9. Blood

0. Normal
1. Mild. Anaemia only
2. Moderate. Asymptomatic pancytopenia
3. Severe. Pancytopenia requiring regular transfusion / transplantation

Section III: Current Clinical Assessment

Rate current status according to the clinician’s examination at the time of assessment unless otherwise stated in the question.

1. Growth (weight) over preceding 6 months

0. Normal. Following normal growth trajectory
1. Mild. Weight less than second centile but growing parallel to it
2. Moderate. Weight crossing one centile
3. Severe. Weight crossing ≥ 2 centiles or less than 2nd centile with divergent trajectory

2. Development over preceding 4 months Score: ____

3. Vision

0. Normal. Normal fixation and tracking
1. Mild. Impaired fixation and / or tracking of small objects
2. Moderate. Impaired fixation and / or tracking of familiar faces
3. Severe. No response to light or registered blind

4. Ptosis and Eye Movement

0. Normal
1. Mild. Gaze evoked nystagmus or unilateral ptosis or impaired eye movement at extremities
2. Moderate. Intermittent nystagmus at rest or bilateral ptosis not obscuring pupils or restriction of >50% eye movement
3. Severe. Continuous nystagmus at rest or bilateral ptosis obscuring pupils or only a flicker of eye movement

5. Myopathy

0. Normal
1. Mild. Mild symmetrical weakness of hip and / or shoulder girdle only
2. Moderate. Moderate symmetrical weakness (proximal > distal) limiting functional movement
3. Severe. Wheelchair / carrier dependent or respiratory compromise due to myopathy.

6. Pyramidal

0. Normal
1. Mild. Unilateral pyramidal signs but retaining functional movement
2. Moderate. Dense hemiplegia with little movement of affected side
3. Severe. Bilateral pyramidal weakness with little or no movement

7. Extrapyramidal

0. Normal.
1. Mild. Unilateral extrapyramidal posturing and increased tone
2. Moderate. Bilateral extrapyramidal posturing and increased tone
3. Severe. Severe extrapyramidal posturing resulting in very little movement

8. Neuropathy

0. Normal.
1. Mild. Areflexia only
2. Moderate. Sensory ataxia or motor impairment (distal weakness) but mobile
3. Severe. Reliant on mobility aids primarily due to neuropathy

Section IV: Quality of Life

This survey asks for your views about your child’s recent health. Please answer every question by marking an ‘x’ in the box next to the phrase which best describes your answer.

1) During the past 4 weeks, how would you rate your child’s overall health?

[ ] Very poor

[ ] Poor

[ ] Fair

[ ] Good

[ ] Very good

2) During the past 4 weeks, how much did your child’s physical health problems limit their physical activities (such as moving or playing)?

[ ] Very much

[ ] Quite a lot

[ ] Somewhat

[ ] A little

[ ] Not at all

3) During the past 4 weeks, how much energy did your child have?

[ ] None

[ ] A little

[ ] Some

[ ] Quite a lot

[ ] Very much

4) During the past 4 weeks, how much bodily pain / discomfort did your child have?

[ ] Very much

[ ] Quite a lot

[ ] Some

[ ] A little

[ ] None

5) During the past 4 weeks, how would you rate your child’s behaviour compared with other children his / her age?

[ ] Very poor

[ ] Poor

[ ] Fair

[ ] Good

[ ] Very good

6) During the past 4 weeks, how would you rate your child’s ability to interact with other people (e.g. with you, siblings or other children his / her age) compared with other children his / her age?

[ ] Very poor

[ ] Poor

[ ] Fair

[ ] Good

[ ] Very good

7) During the past 4 weeks, how much were you (the parent / carer) bothered by emotional problems (e.g. feelings of anxiety, sadness) as a result of your child’s illness?

[ ] Very

[ ] Quite a lot

[ ] Somewhat

[ ] A little

[ ] Not at all

8) During the past 4 weeks, how much was your time limited as a result of your child’s illness?

[ ] Very

[ ] Quite a lot

[ ] Somewhat

[ ] A little

[ ] Not at all

9) During the past 4 weeks, how much were your family’s activities limited or interrupted as a result of your child’s illness?

[ ] Very

[ ] Quite a lot

[ ] Somewhat

[ ] A little

[ ] Not at all

10) During the past 6 months, what has been the financial cost of your child’s illness?

[ ] Very expensive

[ ] Quite expensive

[ ] Moderately expensive

[ ] Little additional cost

[ ] No additional cost

11) During the past 4 weeks, how would you rate your family’s ability to get along with one another?

[ ] Very poor

[ ] Poor

[ ] Fair

[ ] Good

[ ] Very good

12) During the past 4 weeks, how often did your child’s illness have a positive effect on your child, you or your family (e.g. being treated well due to illness, meeting new people)?

[ ] Never

[ ] Occasionally

[ ] Sometimes

[ ] Quite a lot

[ ] Most of the time