Loading…

Protocol - Disease Progression and Regression - Adult

Add to Toolkit

Protocol Name from Source:

This section will be completed when reviewed by an Expert Review Panel.

Availability:

Publicly available

Description:

The Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) and the Newcastle Mitochondrial Disease Adult Scale (NMDAS) can be used to evaluate the progression of mitochondrial disease. There are three versions of the NPMDS, each for a specific age range (0-24 months, 2-11 years, and 12-18 years). The NMDAS is for adult patients over 16 years. The investigators from Newcastle University recommend that if the child experiences early onset of a mitochondrial disease in childhood, the NPMDS 12-18 year scale should be used. If an adolescent experiences onset of a mitochondrial disease, the investigators recommend switching to the NMDAS scale at 16 years.

The aim of the scales is to allow for standardization of patient assessment and to improve accurate data collection. The scales are composed of multiple domains: Current Function, System Specific Involvement, Current Clinical Assessment, and Quality of Life. Almost all questions provide a score which ranges from 0-3, with the following representations: 0 is normal, 1 is mild, 2 is moderate, and 3 is severe. Examples of the severity for each question are provided. Depending on the domain, the questions are either self- or interviewer-administrated, based on a provider’s clinical assessment or medical records. There is a manual for each scale, which details the administration, process, and scoring instructions.

Protocol:

The Newcastle Mitochondrial Disease Adult Scale (NMDAS)

Name: ________________

Date of birth: ________________

Date of assessment: ________________

􀀀 Height: ____________

Forced Vital Capacity (FVC):

􀀀 FVC - 1st attempt ____________

􀀀 FVC - 2nd attempt ____________

􀀀 FVC - 3rd attempt ____________

Section I- Current Function

Rate function over the preceding 4 week period, according to patient and/or caregiver interview only. The clinician’s subjective judgement of functional ability should not be taken into account.

1. Vision with usual glasses or contact lenses

  1. Normal.
  2. No functional impairment but aware of worsened acuities.
  3. Mild - difficulty with small print or text on television.
  4. Moderate - difficulty outside the home (eg bus numbers, road signs or shopping).
  5. Severe - difficulty recognising faces.
  6. Unable to navigate without help (eg carer, dog, cane).

2. Hearing with or without hearing aid

  1. Normal.
  2. No communication problems but aware of tinnitus or deterioration from prior ‘normal’ hearing.
  3. Mild deafness (eg missing words in presence of background noise). Fully corrected with hearing aid.
  4. Moderate deafness (eg regularly requiring repetition). Not fully corrected with hearing aid.
  5. Severe deafness - poor hearing even with aid (see 3 above).
  6. End stage - virtually no hearing despite aid. Relies heavily on non-verbal communication (eg lip reading) or has cochlear implant.

3. Speech

  1. Normal.
  2. Communication unaffected but patient or others aware of changes in speech patterns or quality.
  3. Mild difficulties - usually understood and rarely asked to repeat things.
  4. Moderate difficulties - poorly understood by strangers and frequently asked to repeat things.
  5. Severe difficulties - poorly understood by family or friends.
  6. Not understood by family or friends. Requires communication aid.

4. Swallowing

  1. Normal.
  2. Mild - sensation of solids ‘sticking’ (occasional).
  3. Sensation of solids ‘sticking’ (most meals) or need to modify diet (eg avoidance of steak/salad).
  4. Difficulty swallowing solids - affecting meal size or duration. Coughing, choking or nasal regurgitation infrequent (1 to 4 times per month) but more than peers.
  5. Requires adapted diet - regular coughing, choking, or nasal regurgitation (more than once per week).
  6. Requiring enteral feeding (eg PEG).

5. Handwriting

  1. Normal.
  2. Writing speed unaffected but aware of increasing untidiness.
  3. Mild - Has to write slower to maintain tidiness/legibility.
  4. Moderate - Handwriting takes at least twice as long or resorts to printing (must previously have used joined writing).
  5. Severe - Handwriting mostly illegible. Printing very slow and untidy (eg ‘THE BLACK CAT’ takes in excess of 30 seconds).
  6. Unable to write. No legible words.

6. Cutting food and handling utensils (irrespective of contributory factors - eg weakness, coordination, cognitive function etc. This is also true for questions 7-10)

  1. Normal.
  2. Slightly slow and/or clumsy but minimal effect on meal duration.
  3. Slow and/or clumsy with extended meal duration, but no help required.
  4. Difficulty cutting up food and inaccuracy of transfer pronounced. Can manage alone but avoids problem foods (eg peas) or carer typically offers minor assistance (eg cutting up steak).
  5. Unable to cut up food. Can pass food to mouth with great effort or inaccuracy. Resultant intake minimal. Requires major assistance.
  6. Needs to be fed.

7. Dressing

  1. Normal.
  2. Occasional difficulties (eg shoe laces, buttons etc) but no real impact on time or effort taken to dress.
  3. Mild - Dressing takes longer and requires more effort than expected at the patient’s age. No help required.
  4. Moderate - Can dress unaided but takes at least twice as long and is a major effort. Carer typically helps with difficult tasks such as shoe laces or buttons.
  5. Severe - Unable to dress without help but some tasks completed unaided.
  6. Needs to be dressed.

8. Hygiene

  1. Normal.
  2. Occasional difficulties only but no real impact on time or effort required.
  3. Mild - hygienic care takes longer but quality unaffected.
  4. Moderate - bathes and showers alone with difficulty or needs bath chair / modifications. Dextrous tasks (eg brushing teeth, combing hair) performed poorly.
  5. Severe - unable to bathe or shower without help. Major difficulty using toilet alone. Dextrous tasks require help.
  6. Dependent upon carers to wash, bathe, and toilet.

9. Exercise Tolerance

  1. Normal.
  2. Unlimited on flat - symptomatic on inclines or stairs.
  3. Able to walk < 1000m on the flat. Restricted on inclines or stairs - rest needed after 1 flight (12 steps).
  4. Able to walk < 500m on the flat. Rest needed after 8 steps on stairs.
  5. Able to walk < 100m on the flat. Rest needed after 4 steps on stairs.
  6. Able to walk < 25m on the flat. Unable to do stairs alone.

10. Gait stability

  1. Normal.
  2. Normal gait - occasional difficulties on turns, uneven ground, or if required to balance on narrow base.
  3. Gait reasonably steady. Aware of impaired balance. Occasionally off balance when walking.
  4. Unsteady gait. Always off balance when walking. Occasional falls. Gait steady with support of stick or person.
  5. Gait grossly unsteady without support. High likelihood of falls. Can only walk short distances (< 10m) without support.
  6. Unable to walk without support. Falls on standing.

Section II - System Specific Involvement

Rate function according to patient and/or caregiver interview and consultation with the medical notes. Each inquiry should take into account the situation for the preceding 12 month period only, unless otherwise stated in the question.

1. Psychiatric

  1. None.
  2. Mild & transient (eg reactive depression) - lasting less than 3 months.
  3. Mild & persistent (lasting more than 3 months) or recurrent. Patient has consulted GP.
  4. Moderate & warranting specialist treatment (e.g. from a psychiatrist) - eg. bipolar disorder or depression with vegetative symptoms (insomnia, anorexia, abulia etc).
  5. Severe (eg self harm - psychosis etc).
  6. Institutionalised or suicide attempt.

2. Migraine Headaches During the last 3 months, how many days have headaches prevented the patient from functioning normally at school, work, or in the home?

  1. No past history.
  2. Asymptomatic but past history of migraines.
  3. One day per month.
  4. Two days per month.
  5. Three days per month.
  6. Four days per month or more.

3. Seizures

  1. No past history.
  2. Asymptomatic but past history of epilepsy.
  3. Myoclonic or simple partial seizures only.
  4. Multiple absence, complex partial, or myoclonic seizures affecting function or single generalized seizure.
  5. Multiple generalised seizures.
  6. Status epilepticus.

4. Stroke-like episodes (exclude focal deficits felt to be of vascular aetiology)

  1. None.
  2. Transient focal sensory symptoms only (less than 24 hours).
  3. Transient focal motor symptoms only (less than 24 hours).
  4. Single stroke-like episode affecting one hemisphere (more than 24 hours).
  5. Single stroke-like episode affecting both hemispheres (more than 24 hours).
  6. Multiple stroke-like episodes (more than 24 hours each).

5. Encephalopathic Episodes

  1. No past history.
  2. Asymptomatic but past history of encephalopathy.
  3. Mild - single episode of personality or behavioural change but retaining orientation in time/place/person.
  4. Moderate - single episode of confusion or disorientation in time, place or person.
  5. Severe - multiple moderate episodes (as above) or emergency hospital admission due to encephalopathy without associated seizures or stroke-like episodes.
  6. Very severe - in association with seizures, strokes or gross lactic acidaemia.

6. Gastro-intestinal symptoms

  1. None.
  2. Mild constipation only or past history of bowel resection for dysmotility.
  3. Occasional symptoms of ‘irritable bowel’ (pain, bloating or diarrhoea) with long spells of normality.
  4. Frequent symptoms (as above) most weeks or severe constipation with bowels open less than once/week or need for daily medications.
  5. Dysmotility requiring admission or persistent and/or recurrent anorexia/vomiting/weight loss.
  6. Surgical procedures or resections for gastrointestinal dysmotility.

7. Diabetes mellitus

  1. None
  2. Past history of gestational diabetes or transient glucose intolerance related to intercurrent illness.
  3. Impaired glucose tolerance (in absence of intercurrent illness).
  4. NIDDM (diet).
  5. NIDDM (tablets).
  6. DM requiring insulin (irrespective of treatment at onset).

8. Respiratory muscle weakness

  1. FVC normal (≥ 85% predicted).
  2. FVC < 85% predicted.
  3. FVC < 75% predicted.
  4. FVC < 65% predicted.
  5. FVC < 55% predicted.
  6. FVC < 45% predicted or ventilator support for over 6 hours per 24 hr period (not for OSA alone).

9. Cardiovascular system

  1. None.
  2. Asymptomatic ECG change.
  3. Asymptomatic LVH on echo or non-sustained brady/tachyarrhythmia on ECG.
  4. Sustained or symptomatic arrhythmia, LVH or cardiomyopathy. Dilated chambers or reduced function on echo. Mobitz II AV block or greater.
  5. Requires pacemaker, defibrillator, arrhythmia ablation, or LVEF < 35% on echocardiogram.
  6. Symptoms of left ventricular failure with clinical and/or x-ray evidence of pulmonary oedema or LVEF < 30% on echocardiogram.

Section III - Current Clinical Assessment

Rate current status according to examination performed at the time of assessment

1. Visual acuity with usual glasses, contact lenses or pinhole.

  1. CSD ≤ 12 (ie normal vision - 6/6, 6/6 or better).
  2. CSD ≤ 18 (eg 6/9, 6/9).
  3. CSD ≤ 36 (eg 6/12, 6/24).
  4. CSD ≤ 60 (eg 6/24, 6/36).
  5. CSD ≤ 96 (eg 6/60, 6/36).
  6. CSD ≥ 120 (eg 6/60, 6/60 or worse).

2. Ptosis

  1. None.
  2. Mild ptosis - not obscuring either pupil.
  3. Unilateral ptosis obscuring < 1/3 of pupil.
  4. Bilateral ptosis obscuring < 1/3 or unilateral ptosis obscuring > 1/3 of pupil or prior unilateral surgery.
  5. Bilateral ptosis obscuring > 1/3 of pupils or prior bilateral surgery.
  6. Bilateral ptosis obscuring >2/3 of pupils or >1/3 of pupils despite prior bilateral surgery.

3. Chronic Progressive External Ophthalmoplegia

  1. None.
  2. Some restriction of eye movement (any direction). Abduction complete.
  3. Abduction of worst eye incomplete.
  4. Abduction of worst eye below 60% of normal.
  5. Abduction of worst eye below 30% of normal.
  6. Abduction of worst eye minimal (flicker).

4. Dysphonia/Dysarthria

  1. None.
  2. Minimal - noted on examination only.
  3. Mild - clear impairment but easily understood.
  4. Moderate - some words poorly understood and infrequent repetition needed.
  5. Severe - many words poorly understood and frequent repetition needed.
  6. Not understood. Requires communication aid.

5. Myopathy

  1. Normal.
  2. Minimal reduction in hip flexion and/or shoulder abduction only (eg MRC 4+/5).
  3. Mild but clear proximal weakness in hip flexion and shoulder abduction (MRC 4/5). Minimal weakness in elbow flexion and knee extension (MRC 4+/5 - both examined with joint at 90 degrees).
  4. Moderate proximal weakness including elbow flexion & knee extension (MRC 4/5 or 4 -/5) or difficulty rising from a 90 degree squat.
  5. Waddling gait. Unable to rise from a 90 degree squat (=a chair) unaided.
  6. Wheelchair dependent primarily due to proximal weakness.

6. Cerebellar ataxia

  1. None.
  2. Normal gait but hesitant heel-toe.
  3. Gait reasonably steady. Unable to maintain heel-toe walking or mild UL dysmetria.
  4. Ataxic gait (but walks unaided) or UL intention tremor & past-pointing. Unable to walk heel-toe - falls immediately.
  5. Severe - gait grossly unsteady without support or UL ataxia sufficient to affect feeding.
  6. Wheelchair dependent primarily due to ataxia or UL ataxia prevents feeding.

7. Neuropathy

  1. None.
  2. Subtle sensory symptoms or areflexia.
  3. Sensory impairment only (eg glove & stocking sensory loss).
  4. Motor impairment (distal weakness) or sensory ataxia.
  5. Sensory ataxia or motor effects severely limit ambulation.
  6. Wheelchair bound primarily due to sensory ataxia or neurogenic weakness.

8. Pyramidal Involvement

  1. None.
  2. Focal or generalised increase in tone or reflexes only.
  3. Mild focal weakness, sensory loss or fine motor impairment (eg cortical hand).
  4. Moderate hemiplegia allowing unaided ambulation or dense UL monoplegia.
  5. Severe hemiplegia allowing ambulation with aids or moderate tetraplegia (ambulant).
  6. Wheelchair dependant primarily due to hemiplegia or tetraplegia.

9. Extrapyramidal

  1. Normal.
  2. Mild and unilateral. Not disabling (H&Y stage 1).
  3. Mild and bilateral. Minimal disability. Gait affected (H&Y stage 2).
  4. Moderate. Significant slowing of body movements (H&Y stage 3)
  5. Severe. Rigidity and bradykinesia. Unable to live alone. Can walk to limited extent (H&Y stage 4).
  6. Cannot walk or stand unaided. Requires constant nursing care (H&Y stage 5).

10. Cognitition

Patients undergo testing using WTAR, Symbol Search and Speed of Comprehension Test.

  1. Combined centiles 100 or more.
  2. Combined centiles 60 - 99
  3. Combined centiles 30 - 59
  4. Combined centiles 15 - 29
  5. Combined centiles 5 - 14
  6. Combined centiles 4 or below.

Personnel and Training Required

Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) and the Newcastle Mitochondrial Disease Adult Scale (NMDS) should be administered by clinicians, preferably with experience in caring for patients with mitochondrial disease.

Equipment Needs

None.

Requirements

Requirement CategoryRequired
Average time of greater than 15 minutes in an unaffected individualYes
Major equipmentNo
Specialized requirements for biospecimen collectionNo
Specialized trainingYes

Mode of Administration

Self-administered

Life Stage:

Adolescent, Adult

Specific Instructions:

To maximize consistency, the authors of the scales state it is essential that clinicians adhere to the scale instructions. They also advise that the scales be administrated by clinicians with experience in the care of patients with mitochondrial disease and that the scale is given every 6 months for children under 2 years of age and at 6- to 12-month intervals for older children and adults.

Research Domain Information

Release Date:

April 30, 2015

Definition

This measure determines the impact of disease on an individual over time.

Purpose

This measure is used to assess the presence and degree of symptoms over time. Rare genetic diseases, such as mitochondrial disorders and mucopolysaccharidosis (MPS), can be associated with symptoms that become more severe over time and may result in a regression of some physical abilities. This measure can be used to quantify such changes to determine the natural course of disease(s) as well as contribute to longitudinal or therapeutic intervention studies.

Selection Rationale

The Rare Genetic Conditions Working Group (WG) selected the Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) and the Newcastle Mitochondrial Disease Adult Scale (NMDAS) because mitochondrial disorders have a wide array of symptoms making this measure potentially extensible to other progressive disorders. In addition, rare genetic disorders can be associated with secondary mitochondrial dysfunction and overlapping symptoms. Although these scales were developed for mitochondrial diseases, the WG acknowledges that data from these scales can be beneficial for other rare genetic conditions, such as inborn errors of metabolism, storage disorders, and nonmitochondrial myopathies.

Language

English

Standards

StandardNameIDSource
Common Data Elements (CDE)Adult Disease Progression and Regression Assessment Scale4798112CDE Browser

Process and Review

This section will be completed when reviewed by an Expert Review Panel.

Source

Newcastle University. Newcastle Mitochondrial Disease Adult Scale (NMDAS).

12-18 years. Available at bsu.ncl.ac.uk/pdfs/nmdas_scale.pdf.

General References

Enns, G. M., Moore, T., Le, A., Atkuri, K., Shah, M. K., Cusmano-Ozog, K., Niemi, A. K., & Cowan, T. M. (2014). Degree of glutathione deficiency and redox imbalance depend on subtype of mitochondrial disease and clinical status. PLoS One, 9(6), e100001. doi:10.1371/journal.pone.0100001

Schaefer, A. M., Phoenix, C., Elson, J. L., McFarland, R., Chinnery, P. F., & Turnbull, D. M. (2006). Mitochondrial disease in adults: A scale to monitor progression and treatment. Neurology, 66(12), 1932-1934.

Protocol ID:

220704

Variables:

Export Variables
Variable NameVariable IDVariable DescriptionVersiondbGaP Mapping
PX220704_Mitochondrial_Disease_Adult_NamePX220704010000Full Name4N/A
PX220704_Mitochondrial_Disease_Adult_DOBPX220704020000Date of Birth4N/A
PX220704_Mitochondrial_Disease_Adult_DatePX220704030000Today's Date4N/A
PX220704_Mitochondrial_Disease_Adult_HeightPX220704040000Height4N/A
PX220704_Mitochondrial_Disease_Adult_FVC1PX220704050000Forced Vital Capicity - 1st attempt4N/A
PX220704_Mitochondrial_Disease_Adult_FVC2PX220704060000Forced Vital Capicity - 2nd attempt4N/A
PX220704_Mitochondrial_Disease_Adult_FVC3PX220704070000Forced Vital Capicity - 3rd attempt4N/A
PX220704_Mitochondrial_Disease_Adult_Current_VisionPX220704080000Rate function over the preceding 4 week period, according to patient and/or caregiver interview only. - Vision usual glasses or contact lenses4N/A
PX220704_Mitochondrial_Disease_Adult_Current_HearingPX220704090000Rate function over the preceding 4 week period, according to patient and/or caregiver interview only. - Hearing with or without hearing aid4N/A
PX220704_Mitochondrial_Disease_Adult_Current_SpeechPX220704100000Rate function over the preceding 4 week period, according to patient and/or caregiver interview only. - Speech4N/A
PX220704_Mitochondrial_Disease_Adult_Current_SwallowingPX220704110000Rate function over the preceding 4 week period, according to patient and/or caregiver interview only. - Swallowing4N/A
PX220704_Mitochondrial_Disease_Adult_CurrentHandwritingPX220704120000Rate function over the preceding 4 week period, according to patient and/or caregiver interview only. - Handwriting4N/A
PX220704_Mitochondrial_Disease_Adult_Current_CuttingFoodPX220704130000Rate function over the preceding 4 week period, according to patient and/or caregiver interview only. - Cutting food and handling utensils (irrespective of contributory factors ¿¿¿ eg weakness, coordination, cognitive function etc. This is also true for questions 7-10)4N/A
PX220704_Mitochondrial_Disease_Adult_Current_DressingPX220704140000Rate function over the preceding 4 week period, according to patient and/or caregiver interview only. - Dressing4N/A
PX220704_Mitochondrial_Disease_Adult_Current_HygienePX220704150000Rate function over the preceding 4 week period, according to patient and/or caregiver interview only. - Hygiene4N/A
PX220704_Mitochondrial_Disease_Adult_Current_ExerciseTolerancePX220704160000Rate function over the preceding 4 week period, according to patient and/or caregiver interview only. - Exercise Tolerance4N/A
PX220704_Mitochondrial_Disease_Adult_Current_GaitStabilityPX220704170000Rate function over the preceding 4 week period, according to patient and/or caregiver interview only. - Gait Stability4N/A
PX220704_Mitochondrial_Disease_Adult_System_PsychiatricPX220704180000System Specific Inviolvment - Each inquiry should take into account the situation for the preceding 12 month period only, unless otherwise stated in the question. - Psychiatric4N/A
PX220704_Mitochondrial_Disease_Adult_System_MigrainePX220704190000System Specific Inviolvment - Each inquiry should take into account the situation for the preceding 12 month period only, unless otherwise stated in the question. - Migraine Headaches During the last 3 months, how many days have headaches prevented the patient from functioning normally at school, work, or in the home?4N/A
PX220704_Mitochondrial_Disease_Adult_System_SeizuresPX220704200000System Specific Inviolvment - Each inquiry should take into account the situation for the preceding 12 month period only, unless otherwise stated in the question. - Seizures4N/A
PX220704_Mitochondrial_Disease_Adult_System_StrokeEpisodesPX220704210000System Specific Inviolvment - Each inquiry should take into account the situation for the preceding 12 month period only, unless otherwise stated in the question. - Stroke-like episodes (exclude focal deficits felt to be of vascular aetiology)4N/A
PX220704_Mitochondrial_Disease_Adult_System_EncephalopathicPX220704220000System Specific Inviolvment - Each inquiry should take into account the situation for the preceding 12 month period only, unless otherwise stated in the question. - Encephalopathic Episodes4N/A
PX220704_Mitochondrial_Disease_Adult_System_GastroPX220704230000System Specific Inviolvment - Each inquiry should take into account the situation for the preceding 12 month period only, unless otherwise stated in the question. - Gastro-intestinal symptoms4N/A
PX220704_Mitochondrial_Disease_Adult_System_DiabetesPX220704240000System Specific Inviolvment - Each inquiry should take into account the situation for the preceding 12 month period only, unless otherwise stated in the question. - Diabetes mellitus4N/A
PX220704_Mitochondrial_Disease_Adult_System_RespiratoryMuscle_WeaknessPX220704250000System Specific Inviolvment - Each inquiry should take into account the situation for the preceding 12 month period only, unless otherwise stated in the question. - Respiratory muscle weakness4N/A
PX220704_Mitochondrial_Disease_Adult_System_CardiovascularPX220704260000System Specific Inviolvment - Each inquiry should take into account the situation for the preceding 12 month period only, unless otherwise stated in the question. - Cardiovascular system4N/A
PX220704_Mitochondrial_Disease_Adult_CurrentClinical_VisualAcuityPX220704270000Rate current status according to examination performed at the time of assessment. Visual acuity with usual glasses, contact lenses or pinhole.4N/A
PX220704_Mitochondrial_Disease_Adult_CurrentClinical_PtosisPX220704280000Rate current status according to examination performed at the time of assessment. Ptosis4N/A
PX220704_Mitochondrial_Disease_Adult_CurrentClinical_CPEOPX220704290000Rate current status according to examination performed at the time of assessment. Chronic Progressive External Ophthalmoplegia4N/A
PX220704_Mitochondrial_Disease_Adult_CurrentClinical_DystoniaDysarthriaPX220704300000Rate current status according to examination performed at the time of assessment. Dysphonia/Dysarthria4N/A
PX220704_Mitochondrial_Disease_Adult_CurrentClinical_MyopathyPX220704310000Rate current status according to examination performed at the time of assessment. Myopathy4N/A
PX220704_Mitochondrial_Disease_Adult_CurrentClinical_CerebellarAtaxiaPX220704320000Rate current status according to examination performed at the time of assessment. Cerebellar ataxia4N/A
PX220704_Mitochondrial_Disease_Adult_CurrentClinical_NeuropathyPX220704330000Rate current status according to examination performed at the time of assessment. Neuropathy4N/A
PX220704_Mitochondrial_Disease_Adult_CurrentClinical_PyramidalPX220704340000Rate current status according to examination performed at the time of assessment. Pyramidal Involvement4N/A
PX220704_Mitochondrial_Disease_Adult_CurrentClinical_ExtrapyramidalPX220704350000Rate current status according to examination performed at the time of assessment. Extrapyramidal4N/A
PX220704_Mitochondrial_Disease_Adult_CurrentClinical_CognitionPX220704360000Rate current status according to examination performed at the time of assessment. Cognition4N/A