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Table 1 Clinical features and treatment details

From: Treatment with metformin in twelve patients with Lafora disease

Clinical Features

Pre-Treatment Assessment

Metformin Treatment

Pt

Age (y), Sex

Onset age (y)

Mutationa

Disease duration (y)

Concomitant AEDs

No. GTCS (last 28 days)

Myoclonusb

Disability scalec

Maximal dose (mg), adjusted dose (mg)

Outcome

Duration (months)

Adverse events

1

17d, F

13

EPM2A: c.491 T > G (p.Ile164Ser), c.539 T > C (p.Leu180Pro)

4

VPA, ZNS, PB

0e

+++

4

3000, 1500

Mild improvement (see text)

6

Diarrhoea

2

21, M

16

NHRLC1: c.436G > A (p.Asp146Asn), c.1133 T > C (p.Leu378Pro)

4

VPA, LEV, PERf, CNZ, CLB

18

+

3

2000, 1000

Seizure-freedom, improved cognition, lasted for 6 months

9

Diarrhoea

3g

25, F

13

EPM2A: c.243_246del (p.Asp82Argfs*7)

10

VPA, LEV, ZNS, PB, CNZ

3

+++

4

500, 500

Disease progression

12h

None

4g

19, F

10

NHLRC1: c.205C > G (p.Pro69Ala); c.826_829dup (p.Ala277Aspfs*23)

7

VPA, LEV, ZNS, CNZ

6

+++

4

1000, 500

Disease progression

24

Asthenia

5

17,F

13

NHLRC1: c.205C > G (p.Pro69Ala)

3

VPA, LEV, PER, CNZ

8

+++

4

2000, 2000

Disease progression

13

None

6

23, M

14

EPM2A: c.721C > T (p.Arg241*)

7

LEV, TPM, ZNS

7

+++

4

2000, 2000

Disease progression

9h

Elevated CPK, muscle cramps

7

23, M

10

EPM2A: c.721C > T (p.Arg241*)

11

VPA, PB, PHT, PER, CNZ

11

+++

3

2000, 2000

Disease progression

28

None

8

18, M

14

NHLRC1: c.992del (p.Gly331Glufs*3)

2

VPA, LEV, PER

2

++

2

1700, 500

Disease progression

26

Diarrhoea

9

22, F

13

NHLRC1: c.992del (p.Gly331Glufs*3)

7

VPA, ZNS, PER

3

+++

4

1700, 500

Disease progression

26

Diarrhoea

10

50, F

18

EPM2A: c.721C > T (p.Arg241*), c.835G > A (p.Gly279Ser)

29

VPA, LEV, ZNS, CNZ

1

+++

4

1000, 1000

Mild improvement (see text)

36

None

11

19, F

11

EPM2A: c.323G > T (p.Arg108Leu)

7

VPA, PB, PER, CNZ

0.5

+++

4

1000, 1000

Disease progression

12

None

12

18, M

13

NHLRC1: c.436G > A (p.Asp146Asn), c.1133 T > C (p.Leu378Pro)

4

VPA, LEV, ZNS, PB

3

++

3

1500, 1500

Disease progression

12

None

  1. Legend: AED antiepileptic drug, CLB clobazam, CNZ clonazepam, GTCS generalized tonic-clonic seizures, LD Lafora disease, LEV levetiracetam, PB phenobarbital, PER perampanel, PHT phenytoin, TPM topiramate, VPA valproate, ZNS zonisamide
  2. aWhen only one variant is indicated, this is intended as homozygous. EPM2A RefSeq ID: NM_005670.4; NHLRC1 RefSeq: NM_198586.2
  3. bMyoclonus severity: +, mild myoclonus, i.e. does not interfere with activities of daily living; ++, moderate myoclonus, i.e. interferes with activities of daily living but not with deambulation; +++, severe myoclonus, i.e. interferes with deambulation
  4. cDisability scale developed by Franceschetti et al. [18]: 1, mild cognitive and motor impairment, preserved daily living activities, and social interaction; 2, moderate mental decline, limitations in motor activities and limited social interaction; 3, severe mental and motor impairment, needing help in walking and regular assistance in daily activity, and poor social interaction; 4, patient weelchair-bound or bedridden, and no significant daily living activities or social interaction
  5. ddeceased
  6. ethe patient did not present any GTCS but had 4 prolonged myoclonic seizures in 28 days requiring benzodiazepine rescue medications
  7. fperampanel was introduced at the same time as metformin
  8. gpreviously published in Ref. [19]
  9. hsuspended