Patent Description:
First line treatment for PD is generally by drug therapy using dopamine replacement medications. Once the right dose for each person is established the medication generally is controlling the symptoms of Parkinson's. Over time however; the effects of drugs often are no longer sufficient to manage the symptoms. Side effects can develop along with disease progression. PD treatment traditionally has been to manage symptoms, not to modify the disease by slowing or stopping it or to create any neuro-protections. Patients diagnosed since <NUM> years with PD consume on average a dose of <NUM> till up over <NUM> max. of dopamineregic drugs, with the danger of a severe side effect, known as "freezing", where the patient is suddenly in a paralysis, unable to move forward, which makes it desirable to keep the necessary medication as low as possible.

Although Parkinson's disease is known since more than <NUM> years, no cure is available, but several approaches of treatment are on market and under evaluation, where invasive and non-invasive methods are applied.

Invasive methods mainly are DBS (deep brain stimulation ) and stem cell therapies, non-invasive therapies mostly use sound or magnetic and electric waves to stimulate brain cells. Examples of common non-invasive therapies are electro-magnetic-based Transcranial Magnetic Stimulation (TMS), in which the nerve cells in the brain are activated or even inhibited via magnetic fields, or Transcranial Puls Stimulation ( TPS ) applying light pulses on a limited skull area to stimulate nerve cells, or Focused Ultra Sonic (FUS) therapy, mechanically interrupting nerve channels responsible for uncontrolled hand tremor by overheating a focused brain area to destroy specific nerve cells.

A specific non-invasive therapy for wound-healing, skin-treatment, pain relieve, hair-grow is using semiconductor emitters like Light Emitting Diodes (LED) or Vertical Cavity Surface Emitting Laser (VCSEL), mostly with visible and near infra-red light spectrum, and named as Low-Light-Level-Theraypy (LLLT), Photo-Bio-Modulation Therapy ( PBMT ) and other termini, covering all the same approach: influencing cell beneficial behavior by light.

The influence of red or near infrared- as well as blue light on mammalian cells is observed as supporting element for the production of Adenosine Tri Phosphate (ATP), which is commonly referred to as the "power house" or "energy currency" of the cell, as it provides energy, and breakdown of ATP through hydrolysis, serves a broad range of functions in the cell, including signaling and DNA/RNA synthesis, where the influence of absorbance of photogenic energy on the signaling pathway of exosomes is under evaluation, further also leading to a regulation of Reactive Oxygen Species ( ROS ), Nitric Oxide ( NO ) and Inter cellular Calcium ( ICa2+ ).

Boosting additional NO generation light energy of a bandwidth of <NUM> ±<NUM> is known and analyzed in several studies.

Light energy is absorbed by chromophores inside the mitochondria, supporting the Cytochrome C Oxidase ( CCO ) at complex V of the Electron Transport Chain ( ETC ) of the mitochondrion inner membrane converting Adenosine Duo Phosphate ( ADP ) to ATP at the ATP synthase , but not being exclusively primary receptor for near infrared light.

Available animal or human studies are describing beneficial outcome of different irradiation-therapies with light-sources in wavelength range from red- infra-red- and blue light bandwidth, without disclosure of a useful portable device to treat Parkinson patients.

Furthermore, document <CIT> provides a helmet-shaped device configured to irradiate patient's scalp using light in four different wavelength ranges.

On the market are available -Photo-Bio-Modulation-devices, for home-use with portable conception, or stand-alone-design, are based on semi-spherical helmet shaped devices containing single mounted light sources ( LEDs or laser in numbers of at about <NUM> pieces max. ), mostly claiming beneficial hair growth effects, as well as " supporting brain health ", or hand-held therapy-devices with only few irradiation LEDs or lasers, which are placed by a therapist on the head of patients. Even therapy devices constructed by hobbyists, like a bucket containing simple red light LED-stripes are known to be used by patients, and described as " light bucket ".

A FDA approved Clinical Trial ( NCT02175472 )Photo Pharmics Spectramax USA; is using a table-top lamp emitting green/blue light, with outcomes, even questioned by the researcher. Although several animal and human studies showed beneficiary effects on brain injuries as well on Parkinson's disease, current devices are without conception to penetrate skull and brain tissue in a sufficient stimulating way with different power-settings, radiant energy, tight placements of light-sources, and optimized head coverage, together with sequential flashing modes, which is base of underlying invention.

Medical treatment of Parkinson's Disease ( PD ) by trans-cranial irradiation.

The technical problem, solved by underlying invention is to apply irradiation on human head to penetrate hair, scalp, skull and brain tissue in a sufficient depth to ignite biochemical processes, well described in plural studies in vitro as in vivo. Considering optimal power, power-modification, irradiation placement as well as irradiation placement modification, irradiation-wavelength, together with environmental conditions hygienically factors, and wear-ability of the device is the core of disclosed invention.

The invention is comprising a portable-, wearable helmet-shaped head cover <FIG>, containing an outer shell base-ABS part <NUM> , a removable outer-shell top-ABS part <NUM> , with a combined Light Emitting Diode ( LED ) array <FIG> and an integrated LASER module <FIG> , as illustrated in <FIG> a flexible printed circuit board (PCB ) <NUM> , shaped according a spherical cutting pattern to achieve sufficient ventilation slots <NUM> , with an onboard Master Control Unit ( MCU ) <NUM> placed under the removable outer shell top ABS part, as well as sketched in <FIG> includes <NUM> Light Emitting Diodes ( LED ) as non-coherent light sources in bandwidth of <NUM> ±<NUM> <NUM>, <NUM> ±<NUM> <NUM>, <NUM> ±<NUM> <NUM> and <NUM> ±<NUM> <NUM> shown in <FIG>, with drawing of side-view <NUM> and bottom-view <NUM> together with electrical chart of the quadruple light source <NUM> , mounted as single chip on a <NUM> LED socket <NUM> thereafter soldered on a PCB as surface mounted devices (SMD) as shown in <FIG>. An optical grade transparent Polymethyl Methacrylate ( PMMA ) inner shell, <FIG> , protecting the emitting light sources, assuring irradiation without loss and hygienic clean ability for multiple usage.

The device is intended to support sub-cellular neuronal bio-chemical processes leading in reduction of stiffness, movement disorders, and promoting relaxation of muscles, whereas the VCSEL laser adapter at ear delivers normal radiation therapy through the skull, but on nose is intended to breach the blood-brain-barrier( BBB ) allowing drugs delivery via the nasal cavity inside the brain, known as Intranasal Nose-to Brain Delivery. The full size helmet style, shown in <FIG>, is covering forehead, ears, and back head till to neck, with a full irradiation influence on total skull <NUM> emitted bv tight arranged light sources <NUM>.

<FIG> shows the electronic schema of the underlying patent comprising a 12V/<NUM> Ah powerbank <NUM> , an <NUM> bit Advanced RISC Machine ( ARM ) Micro Controller Unit ( MCU ) <NUM> , Touch buttons for power- <NUM> and mode- <NUM> -input, an Unified Serial Bus ( USB ) <NUM> for software update, laser module output for laser modules <NUM> ,<NUM> , the software controlled frequency rhythm <NUM>, power level <NUM>, by Pulse Wide Modulation. <NUM> , a Temperature security shutdown regulator <NUM>, a Timer module <NUM>, a Wi-Fi router <NUM>, communicating through Wi-Fi <NUM> , with controlling devices as PC <NUM>, or Notebook <NUM>, or Smartphone <NUM> , and Tablet <NUM> , operating on Windows, iOS, Linux, and Android software.

<FIG> shows the Graphical User Interface ( GUI ) used to control parameters of the invention like ON / OFF switch <NUM> , full flashing mode, blinking all <NUM> pieces LEDs <NUM> , a flashing mode with diagonal- <NUM>, spiral- <NUM> , rotation <NUM>, strobe- <NUM>, wave- <NUM> irradiation-pattern and rhythm, as well a preset frequency rhythm as fast <NUM> or slow <NUM>. With the slider "power" <NUM> irradiation power is adjusted, with slider " delay" <NUM> , delay time between increment steps of power is selected, with slider " time " <NUM> therapy time is chosen. Electrical values are displayed on scales <NUM> , inside helmet temperature is indicated at scale <NUM> , real time irradiation energy shown on scale <NUM> , transmission channel of actual controlled device ( in simultaneous multi-device / multi-channel operation mode ) is selected by drop-down menu <NUM> , and data recording is activated by switch <NUM>.

<FIG> is a drawing of the flexible PCB inner side <NUM> , which is faced to skull, ( flat, unfolded ) with <NUM> pieces of SMD mounted LED sockets comprising quadruple light sources of totaling <NUM> individual light sources.

<FIG> is a magnified presentation of the flexible PCB inner side ( flat, unfolded ) <NUM> , showing LED socket <NUM> mounted as LED array on a single segment.

<FIG> is a top view of the four light sources <NUM> , <NUM> , <NUM>, and <NUM>, with a side view <NUM>, and bottom view <NUM> of the LED socket, together with their electric symbolic chart <NUM>. Also demonstrating irradiation beams emitted by the quadruple light sources, mounted on a single LED socket <NUM> , illuminating the skull surface <NUM> with symbolized irradiation beam of <NUM> ±<NUM> <NUM> , <NUM> ±<NUM> <NUM> ,<NUM> ±<NUM> <NUM> ,and <NUM> ±<NUM> <NUM>.

<FIG> shows the two ear/ nose laser modules <NUM>, comprising the laser itself <NUM> with Infra-Red wavelength of <NUM> ±<NUM>, together with green indication LED <NUM> , and the electrical symbol chart of laser <NUM><NUM>, laser function-indicator <NUM><NUM>, laser <NUM><NUM> and laser function-indicator <NUM><NUM> , allowing simultaneously the usage of head-, and ear- or nose- irradiation.

<FIG> is showing the outer-, or top-side-flexible PCB, facing away from head, containing <NUM> pieces of frontal segments <NUM>, <NUM> pieces of side and back segments <NUM>, and <NUM> center-top segment <NUM>.

<FIG> shows mounted MCU <NUM> and driver Integrated Circuits ( IC ) <NUM> of center-top-segment.

<FIG> shows a symbolic electrical chart, illustrating " irradiation segment <NUM>" <NUM>, " irradiation segment <NUM> " <NUM> , "irradiation segment <NUM> " <NUM> , and " irradiation segment <NUM> ", as well as laser <NUM><NUM>, indicator <NUM><NUM>, laser <NUM><NUM>, indicator <NUM><NUM>.

<FIG> illustrates the incremental process during power-rise <NUM> , the overlaying <NUM> pulse frequency <NUM> , and the <NUM> pulsing frequency of laser modules <NUM>.

<FIG> shows characteristic wavelength data of LED <NUM> ±<NUM> <NUM>, of LED <NUM> ±<NUM> <NUM>, of LED <NUM> ±<NUM> <NUM> and of LED <NUM> ±<NUM> <NUM>.

<FIG> shows characteristic wavelength data of laser <NUM> ±<NUM> <NUM>, the illumination angle thereof <NUM> , and the typical illumination angle of implemented LEDs.

<FIG> depict the different illumination modes controlled by MCU," rotate "<NUM> , incrementing circular <NUM> segments in cycle, " spiral " <NUM> , incrementing circular segments in cycle," wave " <NUM> , incrementing alternating circular <NUM> segments in cycle," cross " <NUM> , incrementing diagonal segments in cycle," strobe " <NUM> , incrementing randomized segments in cycle," full" <NUM> , pulsing all segments in cycle,.

<FIG> shows the bent flexible PCB covering full forehead, till back to neck, including ears <NUM> , and top mounted MCU <NUM> , constructed to allow ventilation channels <NUM> for cooling.

<FIG> shows the combined wearable helmet cover without the between inner- <NUM> and outer shield <NUM>, mounted flexible PCB.

<FIG> shows the upper- <NUM> , and lower-part <NUM> , of the outer shell of the helmet, which covers the flexible PCB on top.

<FIG> shows the left side of the device with touch button for flash mode selection <NUM> and plug for laser module <NUM>.

<FIG> is the back view with the USB plug <NUM> used for software upload.

<FIG> is the drawing of the inner shell <NUM> , protecting the flexible PCB, manufactured in clear optical PMMA to reduce optical losses to a minimum.

<FIG> shows, in cross section view, the tight assembly of LED light sources <NUM> covering the head from forehead till back to neck, including ears.

<FIG> symbolizes, in cross section view, the deep penetration of light energy till into the brain tissue <NUM> , emitted by light sources <NUM>.

<FIG> demonstrates four different light beams <NUM> , with different wavelength, penetrating between hairs <NUM> , through scalp <NUM>, skull <NUM> and brain tissue <NUM> in different depths, where higher wavelength assures deeper penetration, but blue light activates surface of scalp only. To achieve full penetration in different brain areas <NUM> different wavelength chips, namely <NUM> ±<NUM>, <NUM> ±<NUM>, <NUM> ±<NUM> and <NUM> ±<NUM> are integrated on a single LED socket, delivering high intensity therapeutic <NUM> pulsed photon energy, with a maximum irradiation flux intensity of <NUM> mW/cm<NUM>, <NUM> J/cm<NUM> ( Root Mean Square (RMS)), on a full treatment surface of <NUM><NUM>.

<FIG> shows the bio-chemical reaction caused by the light irradiation in different wavelengths, resulting for example in a positive stimulation of Adenosine Tri Phosphate ( ATP ) production in phase V <NUM> of the Electron Transport Chain ( ETC ) <NUM> on the inner membrane of mitochondria ( <NUM> ), but also stimulating for example Reactive Oxygen Species ( ROS ) or Nitric Oxide ( NO ).

<FIG> is a topographic chart of the brain activities, where lighter color areas <NUM> correspondent to lower, and darker colored areas <NUM> to higher brain activities, measured at <NUM> electrodes, placed according the electrode schemes <NUM>.

<FIG> is showing the result of an Electroencephalogram ( EEG ) analysis, which was recorded before, and after <NUM> irradiation, plotting brainwaves in Alpha bandwidth ( <NUM> - <NUM>) <NUM>, Beta bandwidth ( <NUM> - <NUM> ) <NUM> , Delta Bandwidth ( <NUM> - <NUM> ) <NUM> , and Theta bandwidth ( <NUM>- <NUM> ) <NUM> charted before " pre " <NUM> and after " post" <NUM> irradiation, illustrating a significant increase of Alpha activities, signaling calm stable relaxation without of signs of anxiousness, an increase of Beta activities, especially on forehead demonstrating an awake activity, and slight increase in Theta activity, prescribed as a status of "deep relaxation ", demonstrating positive influence of underlying invention on brain activities after irradiation.

Over a period of more than <NUM> years (November <NUM> -June <NUM>) several systems of red /infra-red and blue light wavelength combinations were explored and tested on <NUM> patients ( <NUM> male, <NUM> female ), and <NUM> control person ( male ), ending up in an optimized quadruple-wavelength version of <NUM> <NUM> <NUM> and <NUM> of irradiation LEDs, and therapy treatment time of <NUM> minutes twice a day
Safety was assessed on the basis of adverse events, regularly observation of behavior, cognition , mobility, dyskinesia, falls, adverse changes in mood, and impulsivity. Treatment Emergent Adverse Events ( TEAEs) were defined as adverse events, starting on or after the date of the first use of radiation device.

Derived from Unified Parkinson's Disease Rating Scale (UDPRS), Hoehn and Yahr Scale, Schwab and England Activities of Daily Living Scale (ADL), and Parkinson's Disease Questionnaire (PDQ-<NUM>) tests and observations were expanded with outdoor activities to get a broader view of patients impairments, abilities and disabilities.

<FIG> is comparing abilities and impairments of <NUM> patients and <NUM> control person.

As in this situation a randomized double-blinded clinical study is not feasible, the study is not fully based on statistical data, but subjective observation, discussions and interviews by the examiner, not all data have quantitative data sets, but major findings and observations at the group attending the radiation therapy, are :.

The invention is comprising a portable-, wearable helmet-shaped head cover, as shown in <FIG> , containing an outer shell base-ABS part <NUM> , a removable outer-shell top-ABS part <NUM> , with a combined Light Emitting Diode ( LED ) array <FIG> emitting incoherent light at a wavelength of between <NUM> and <NUM>, and an integrated LASER module <FIG> emitting coherent infra-red light at a wavelength of <NUM>, as illustrated in <FIG> a flexible printed circuit board ( PCB ) <NUM> , shaped according a spherical cutting pattern to achieve sufficient ventilation slots <NUM> , with an onboard Master Control Unit ( MCU ) <NUM> placed under the removable outer shell top ABS part, as well as sketched in <FIG> includes <NUM> Light Emitting Diodes ( LED ) as non-coherent light sources in bandwidth of <NUM> ±<NUM> <NUM> , <NUM> ±<NUM> <NUM>, <NUM> ±<NUM> <NUM> and <NUM> ±<NUM> <NUM> shown in <FIG>, with drawing of side-view <NUM> and bottom-view <NUM> together with electrical chart of the quadruple light source <NUM> , mounted as single chip on a <NUM> LED socket <NUM> thereafter soldered on a PCB as surface mounted devices (SMD) as shown in <FIG>.

An optical grade transparent Polymethyl Methacrylate ( PMMA ) inner shell, <FIG> , protecting the emitting light sources, assuring irradiation without loss and hygienic clean ability for multiple usage.

Claim 1:
A portable helmet-shaped device configured to cover patient's head, the device comprising
a PCB (<NUM>) and an array including <NUM> non-coherent light sources grouped as quadruple light sources (<NUM>),
wherein each quadruple light source (<NUM>) has an arrangement of four LEDs comprising
a first LED (<NUM>, D1) configured to emit light in a bandwidth of <NUM> ±<NUM>,
a second LED (<NUM>, D2) configured to emit light in a bandwidth of <NUM> ±<NUM>,
a third LED (<NUM>, D3) configured to emit light in a bandwidth of <NUM> ±<NUM> and
a fourth LED (<NUM>, D4) configured to emit light in a bandwidth of <NUM> ±<NUM>,
wherein each said arrangement of four LEDs (<NUM>, <NUM>, <NUM>, <NUM>; D1, D2, D3, D4) is mounted on a single LED socket (<NUM>, <NUM>) being soldered on said PCB (<NUM>) as SMD, and
wherein said array is configured to irradiate patient's head for stimulating bio-chemical effects to ease patient's impairments due to Parkinson's disease.